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Entry
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- *114182 - CALMODULIN 2; CALM2
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- OMIM
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<p>
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<span class="h4">*114182</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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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/114182">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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</ul>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000143933;t=ENST00000272298" 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=805" 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=114182" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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<div 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=ENSG00000143933;t=ENST00000272298" 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_001305624,NM_001305625,NM_001305626,NM_001743" 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_001743" 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=114182" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=00242&isoform_id=00242_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/CALM2" 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/179884,665588,2055425,4262723,4502549,13097165,13623675,14250065,16924229,17391486,19913529,32880175,49456933,49456995,62988698,119620625,119620626,119620627,119620628,189055073,779176942,779176972,779176998,1191692490" 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/P0DP24" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=805" 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=ENSG00000143933;t=ENST00000272298" 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=CALM2" 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=CALM2" 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+805" 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/CALM2" 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:805" 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/805" 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=chr2&hgg_gene=ENST00000272298.12&hgg_start=47160082&hgg_end=47176936&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:1445" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:1445" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=114182[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=114182[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000143933" 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=CALM2" 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=CALM2" 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=CALM2" 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=CALM2&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/PA26038" 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:1445" 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/FBgn0000253.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:103250" 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/CALM2#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:103250" 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/805/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=805" 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=WBGene00000552;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-020415-2" 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:805" 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=CALM2&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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114182
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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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CALMODULIN 2; CALM2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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PHKD2
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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=CALM2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CALM2</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/2/236?start=-3&limit=10&highlight=236">2p21</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:47160082-47176936&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'})">2:47,160,082-47,176,936</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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<a href="/geneMap/2/236?start=-3&limit=10&highlight=236">
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2p21
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Long QT syndrome 15
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/616249"> 616249 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/114182" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/114182" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div>
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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<p>Calmodulin is an essential calcium-sensing, signal-transducing protein. Three calmodulin genes, CALM1 (<a href="/entry/114180">114180</a>), CALM2, and CALM3 (<a href="/entry/114183">114183</a>), have unique nucleotide sequences but encode identical 149-amino acid calmodulin proteins with 4 EF-hand calcium-binding loops. Calcium-induced activation of calmodulin regulates many calcium-dependent processes and modulates the function of cardiac ion channels, including CaV1.2 (CACNA1C; <a href="/entry/114205">114205</a>), NaV1.5 (SCN5A; <a href="/entry/600163">600163</a>), and the ryanodine receptor (RYR2; <a href="/entry/180902">180902</a>) (summary by <a href="#2" class="mim-tip-reference" title="Boczek, N. J., Gomez-Hurtado, N., Ye, D., Calvert, M. L., Tester, D. J., Kryshtal, D. O., Hwang, H. S., Johnson, C. N., Chazin, W. J., Loporcaro, C. G., Shah, M., Papez, A. L., Lau, Y. R., Kanter, R., Knollmann, B. C., Ackerman, M. J. <strong>Spectrum and prevalence of CALM1-, CALM2-, and CALM3-encoded calmodulin variants in long QT syndrome and functional characterization of a novel long QT syndrome-associated calmodulin missense variant, E141G.</strong> Circ. Cardiovasc. Genet. 9: 136-146, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26969752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26969752</a>] [<a href="https://doi.org/10.1161/CIRCGENETICS.115.001323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26969752">Boczek et al., 2016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26969752" 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="#10" class="mim-tip-reference" title="SenGupta, B., Friedberg, F., Detera-Wadleigh, S. D. <strong>Molecular analysis of human and rat calmodulin complementary DNA clones: evidence for additional active genes in these species.</strong> J. Biol. Chem. 262: 16663-16670, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2445749/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2445749</a>]" pmid="2445749">SenGupta et al. (1987)</a> first identified and cloned the second calmodulin gene. <a href="#5" class="mim-tip-reference" title="Fischer, R., Koller, M., Flura, M., Mathews, S., Strehler-Page, M.-A., Krebs, J., Penniston, J. T., Carafoli, E., Strehler, E. E. <strong>Multiple divergent mRNAs code for a single human calmodulin.</strong> J. Biol. Chem. 263: 17055-17062, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3182832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3182832</a>]" pmid="3182832">Fischer et al. (1988)</a> noted that, although the CALM1, CALM2, and CALM3 proteins are identical, at the nucleotide level they share only about 80% identity within their coding regions, and they contain no significant homology within their noncoding regions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2445749+3182832" 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>Using a sequence from CALM3 as probe, <a href="#11" class="mim-tip-reference" title="Toutenhoofd, S. L., Foletti, D., Wicki, R., Rhyner, J. A., Garcia, F., Tolon, R., Strehler, E. E. <strong>Characterization of the human CALM2 calmodulin gene and comparison of the transcriptional activity of CALM1, CALM2, and CALM3.</strong> Cell Calcium 23: 323-338, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9681195/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9681195</a>] [<a href="https://doi.org/10.1016/s0143-4160(98)90028-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9681195">Toutenhoofd et al. (1998)</a> cloned CALM2 from a small intestine mucosa cDNA library. Northern blot analysis revealed a major 1.4-kb transcript in all tissues tested, with highest expression in brain. High levels of expression were also found in heart, placenta, lung, liver, skeletal muscle, and kidney, with lowest levels found in pancreas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9681195" 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="#11" class="mim-tip-reference" title="Toutenhoofd, S. L., Foletti, D., Wicki, R., Rhyner, J. A., Garcia, F., Tolon, R., Strehler, E. E. <strong>Characterization of the human CALM2 calmodulin gene and comparison of the transcriptional activity of CALM1, CALM2, and CALM3.</strong> Cell Calcium 23: 323-338, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9681195/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9681195</a>] [<a href="https://doi.org/10.1016/s0143-4160(98)90028-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9681195">Toutenhoofd et al. (1998)</a> determined that the CALM2 gene contains 6 exons and spans more than 16 kb. Within the 5-prime flanking region, CALM2 contains a TATA-like sequence, a far upstream CCAAT box, several AP1 (<a href="/entry/165160">165160</a>)-, AP2 (see <a href="/entry/107580">107580</a>)-, and CRE (see <a href="/entry/123811">123811</a>)-binding sites, and a repeated AGGGA motif that is found in other CALM genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9681195" 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="#9" class="mim-tip-reference" title="McPherson, J. D., Hickie, R. A., Wasmuth, J. J., Meyskens, F. L., Perham, R. N., Strehler, E. E., Graham, M. T. <strong>Chromosomal localization of multiple genes encoding calmodulin. (Abstract)</strong> Cytogenet. Cell Genet. 58: 1951 only, 1991."None>McPherson et al. (1991)</a> tentatively assigned the CALM2 gene to chromosome 10 by study of somatic cell hybrids. However, by PCR-based amplification of CALM2-specific sequences using DNA from human/hamster cell hybrids as template, <a href="#1" class="mim-tip-reference" title="Berchtold, M. W., Egli, R., Rhyner, J. A., Hameister, H., Strehler, E. E. <strong>Localization of the human bona fide calmodulin genes CALM1, CALM2, and CALM3 to chromosomes 14q24-q31, 2p21.1-p21.3, and 19q13.2-q13.3.</strong> Genomics 16: 461-465, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8314583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8314583</a>] [<a href="https://doi.org/10.1006/geno.1993.1211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8314583">Berchtold et al. (1993)</a> found that the CALM2 gene is located on chromosome 2. They regionalized the gene to 2p21.3-p21.1 by in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8314583" 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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In a Hispanic girl with markedly prolonged QTc intervals and multiple episodes of ventricular fibrillation (LQT15; <a href="/entry/616249">616249</a>), <a href="#3" class="mim-tip-reference" title="Crotti, L., Johnson, C. N., Graf, E., De Ferrari, G. M., Cuneo, B. F., Ovadia, M., Papagiannis, J., Feldkamp, M. D., Rathi, S. G., Kunic, J. D., Pedrazzini, M., Wieland, T., and 11 others. <strong>Calmodulin mutations associated with recurrent cardiac arrest in infants.</strong> Circulation 127: 1009-1017, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23388215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23388215</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23388215[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/10.1161/CIRCULATIONAHA.112.001216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23388215">Crotti et al. (2013)</a> performed exome sequencing and identified a heterozygous de novo missense mutation in the CALM2 gene (D96V; <a href="#0001">114182.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23388215" 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 unrelated patients of varying ancestry with long QT syndrome, <a href="#8" class="mim-tip-reference" title="Makita, N., Yagihara, N., Crotti, L., Johnson, C. N., Beckmann, B.-M., Roh, M. S., Shigemizu, D., Lichtner, P., Ishikawa, T., Aiba, T., Homfray, T., Behr, E. R., and 27 others. <strong>Novel calmodulin mutations associated with congenital arrhythmia susceptibility.</strong> Circ. Cardiovasc. Genet. 7: 466-474, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24917665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24917665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24917665[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/10.1161/CIRCGENETICS.113.000459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24917665">Makita et al. (2014)</a> identified heterozygosity for 5 different de novo missense mutations in the CALM2 gene (<a href="#0002">114182.0002</a>-<a href="#0006">114182.0006</a>). Functional analysis demonstrated significant reductions in calcium-binding affinity with the variants compared to wildtype calmodulin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24917665" 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="#2" class="mim-tip-reference" title="Boczek, N. J., Gomez-Hurtado, N., Ye, D., Calvert, M. L., Tester, D. J., Kryshtal, D. O., Hwang, H. S., Johnson, C. N., Chazin, W. J., Loporcaro, C. G., Shah, M., Papez, A. L., Lau, Y. R., Kanter, R., Knollmann, B. C., Ackerman, M. J. <strong>Spectrum and prevalence of CALM1-, CALM2-, and CALM3-encoded calmodulin variants in long QT syndrome and functional characterization of a novel long QT syndrome-associated calmodulin missense variant, E141G.</strong> Circ. Cardiovasc. Genet. 9: 136-146, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26969752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26969752</a>] [<a href="https://doi.org/10.1161/CIRCGENETICS.115.001323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26969752">Boczek et al. (2016)</a> performed whole-exome sequencing in 38 unrelated LQTS patients who were negative for mutation in 14 known LQTS-associated genes and identified a 14-year-old Indian girl and a 7-year-old white boy who were heterozygous for 2 different missense mutations at the same codon in the CALM2 gene, D130G (<a href="#0007">114182.0007</a>) and D130V, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26969752" 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>Reviews</em></strong></p><p>
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<a href="#4" class="mim-tip-reference" title="Crotti, L., Spazzolini, C., Tester, D. J., Ghidoni, A., Baruteau, A.-E., Beckmann, B.-M., Behr, E. R., Bennet, J. S., Bezzina, C. R., Bhuiyan, Z. A., Celiker, A., Cerrone, M., and 29 others. <strong>Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry.</strong> Europ. Heart J. 40: 2964-2975, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31170290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31170290</a>] [<a href="https://doi.org/10.1093/eurheartj/ehz311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31170290">Crotti et al. (2019)</a> reviewed 74 patients, from the International Calmodulinopathy Registry and from the published literature, who had mutations in the CALM1 (<a href="/entry/114180">114180</a>), CALM2, or CALM3 (<a href="/entry/114183">114183</a>) genes (36, 23, and 15 patients, respectively) and who did not have clinically relevant pathogenic variants in other arrhythmia-susceptibility genes. Sixty-four (86.5%) of the patients were symptomatic, and the 10-year cumulative mortality was 27%. The 2 prevalent phenotypes were LQTS (49%) and CPVT (28%); other diagnoses included idiopathic ventricular fibrillation (10%), sudden unexplained death (5%), and overlapping features of LQTS/CPVT (4%). The majority of variants (80%) affected amino acid residues on the EF-hand Ca(2+)-binding loops III and IV, and almost 90% of them affected 1 of the 4 residues principally involved in Ca(2+) binding (Asp, Asp, Asp/Asn, and Glu, at positions 1, 3, 5, and 12, respectively, from the beginning of each 12-residue loop). Three residues appeared to be relative hotspots, with N98S, D130G, and F142L identified in 10, 5, and 4 families, respectively. The authors noted that LQTS-associated calmodulin variants, located primarily in EF hands III and IV, show a strong dominant-negative reduction in Ca(2+)-dependent inactivation of the L-type Ca(2+) channel Ca(v)1.2 (CACNA1C; <a href="/entry/114205">114205</a>), which results in repolarization delay However, the major effect of CPVT-associated variants, mostly located in either EF hand III or in the inter-EF hand I-II linker, appears to be a higher binding affinity for RyR2 (<a href="/entry/180902">180902</a>), promoting its open conformation and increasing the frequency of Ca(2+) waves. The authors added that no gene-specific phenotypic correlations could be made since mutations in all 3 calmodulin genes may give rise to different phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31170290" 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">rs730882254 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs730882254;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=rs730882254" 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=rs730882254" 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=RCV000162065 OR RCV001547926 OR RCV001850284" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000162065, RCV001547926, RCV001850284" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000162065...</a>
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<p>In a Hispanic girl with markedly prolonged QTc intervals and multiple episodes of ventricular fibrillation (LQT15; <a href="/entry/616249">616249</a>), <a href="#3" class="mim-tip-reference" title="Crotti, L., Johnson, C. N., Graf, E., De Ferrari, G. M., Cuneo, B. F., Ovadia, M., Papagiannis, J., Feldkamp, M. D., Rathi, S. G., Kunic, J. D., Pedrazzini, M., Wieland, T., and 11 others. <strong>Calmodulin mutations associated with recurrent cardiac arrest in infants.</strong> Circulation 127: 1009-1017, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23388215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23388215</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23388215[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/10.1161/CIRCULATIONAHA.112.001216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23388215">Crotti et al. (2013)</a> identified heterozygosity for a de novo A-T transversion in the CALM2 gene, resulting in an asp96-to-val (D96V) substitution at a highly conserved residue in the EF-hand domain III. The mutation was not found in 92 Hispanic American controls or in the dbSNP (build 130), 1000 Genomes Project, Exome Variant Server, or Helmholtz exome databases. Functional analysis demonstrated a 13-fold reduction in calcium-binding affinity with the mutant compared to wildtype calmodulin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23388215" 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="#6" class="mim-tip-reference" title="Gomez-Hurtado, N., Boczek, N. J., Kryshtal, D. O., Johnson, C. N., Sun, J., Nitu, F. R., Cornea, R. L., Chazin, W. J., Calvert, M. L., Tester, D. J., Ackerman, M. J., Knollmann, B. C. <strong>Novel CPVT-associated calmodulin mutation in CALM3 (CALM3-A103V) activates arrhythmogenic Ca waves and sparks.</strong> Circ. Arrhythm. Electrophysiol. 9: e004161, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27516456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27516456</a>] [<a href="https://doi.org/10.1161/CIRCEP.116.004161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27516456">Gomez-Hurtado et al. (2016)</a> studied the CALM2 D96V mutation in permeabilized mouse ventricular myocytes and observed significantly increased L-type calcium channel inactivation time with the mutant compared to wildtype calmodulin. In addition, the D96V mutation dramatically increased the action potential duration at both 50% and 90% of repolarization. Early after-depolarizations were observed in 36% of cardiomyocytes dialyzed with the D96V mutant, which the authors noted was consistent with the clinical phenotype of LQTS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27516456" 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">rs398124650 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398124650;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=rs398124650" 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=rs398124650" 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=RCV000143839 OR RCV000162066" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000143839, RCV000162066" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000143839...</a>
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<p>In a 16-year-old Japanese girl who had fetal bradycardia and episodes of syncope in early childhood and was found to have marked QTc prolongation on electrocardiography (LQT15; <a href="/entry/616249">616249</a>), <a href="#8" class="mim-tip-reference" title="Makita, N., Yagihara, N., Crotti, L., Johnson, C. N., Beckmann, B.-M., Roh, M. S., Shigemizu, D., Lichtner, P., Ishikawa, T., Aiba, T., Homfray, T., Behr, E. R., and 27 others. <strong>Novel calmodulin mutations associated with congenital arrhythmia susceptibility.</strong> Circ. Cardiovasc. Genet. 7: 466-474, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24917665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24917665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24917665[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/10.1161/CIRCGENETICS.113.000459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24917665">Makita et al. (2014)</a> identified heterozygosity for a de novo c.400G-C transversion in exon 5 of the CALM2 gene, resulting in an asp134-to-his (D134H) substitution at a conserved residue within the fourth EF-hand calcium-binding motif in the C-terminal domain. The mutation was not found in her unaffected parents, 2 unaffected brothers, or in the dbSNP, 1000 Genomes Project, Exome Variant Server, RIKEN, or Human Genetic Variation Browser databases. Functional analysis demonstrated a 13-fold reduction in calcium-binding affinity with the D134H mutant compared to wildtype calmodulin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24917665" 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">rs398124647 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398124647;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=rs398124647" 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=rs398124647" 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=RCV000143836 OR RCV000162067 OR RCV003318349" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000143836, RCV000162067, RCV003318349" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000143836...</a>
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<p>In a 12-year-old Japanese boy with episodes of syncope on exertion and QTc prolongation on electrocardiography (LQT15; <a href="/entry/616249">616249</a>), <a href="#8" class="mim-tip-reference" title="Makita, N., Yagihara, N., Crotti, L., Johnson, C. N., Beckmann, B.-M., Roh, M. S., Shigemizu, D., Lichtner, P., Ishikawa, T., Aiba, T., Homfray, T., Behr, E. R., and 27 others. <strong>Novel calmodulin mutations associated with congenital arrhythmia susceptibility.</strong> Circ. Cardiovasc. Genet. 7: 466-474, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24917665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24917665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24917665[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/10.1161/CIRCGENETICS.113.000459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24917665">Makita et al. (2014)</a> identified heterozygosity for a de novo c.293A-G transition in exon 5 of the CALM2 gene, resulting in an asn98-to-ser (N98S) substitution at a conserved residue within the third EF-hand calcium-binding motif in the C-terminal domain. The mutation was not found in his unaffected parents or brother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24917665" 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="#6" class="mim-tip-reference" title="Gomez-Hurtado, N., Boczek, N. J., Kryshtal, D. O., Johnson, C. N., Sun, J., Nitu, F. R., Cornea, R. L., Chazin, W. J., Calvert, M. L., Tester, D. J., Ackerman, M. J., Knollmann, B. C. <strong>Novel CPVT-associated calmodulin mutation in CALM3 (CALM3-A103V) activates arrhythmogenic Ca waves and sparks.</strong> Circ. Arrhythm. Electrophysiol. 9: e004161, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27516456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27516456</a>] [<a href="https://doi.org/10.1161/CIRCEP.116.004161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27516456">Gomez-Hurtado et al. (2016)</a> studied the CALM2 N98S mutation in permeabilized mouse ventricular myocytes and observed significantly increased spark frequency and reduced sarcoplasmic reticulum Ca(2+) content with the mutant compared to wildtype calmodulin. The cardiomyocytes also showed increased spontaneous Ca(2+) release in the form of regular propagated Ca(2+) waves with the mutant compared to wildtype calmodulin, and the mutant demonstrated a dominant effect, with significantly higher Ca(2+) wave frequencies even in the presence of 3-fold excess of wildtype calmodulin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27516456" 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">rs398124647 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398124647;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=rs398124647" 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=rs398124647" 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=RCV000143837 OR RCV000162068" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000143837, RCV000162068" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000143837...</a>
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<p>In a 2.5-year-old English boy who had cardiac arrest due to ventricular fibrillation at 17 months of age, and in whom electrocardiography showed bradycardia and a prolonged QTc interval (LQT15; <a href="/entry/616249">616249</a>), <a href="#8" class="mim-tip-reference" title="Makita, N., Yagihara, N., Crotti, L., Johnson, C. N., Beckmann, B.-M., Roh, M. S., Shigemizu, D., Lichtner, P., Ishikawa, T., Aiba, T., Homfray, T., Behr, E. R., and 27 others. <strong>Novel calmodulin mutations associated with congenital arrhythmia susceptibility.</strong> Circ. Cardiovasc. Genet. 7: 466-474, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24917665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24917665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24917665[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/10.1161/CIRCGENETICS.113.000459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24917665">Makita et al. (2014)</a> identified heterozygosity for a de novo c.293A-T transversion in exon 5 of the CALM2 gene, resulting in an asn98-to-ile (N98I) substitution at a conserved residue within the third EF-hand calcium-binding motif in the C-terminal domain. The mutation was not present in his unaffected parents. Functional analysis demonstrated a 7-fold reduction in calcium-binding affinity with the N98I mutant compared to wildtype calmodulin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24917665" 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">rs398124648 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398124648;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=rs398124648" 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=rs398124648" 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=RCV000143838 OR RCV000162069" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000143838, RCV000162069" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000143838...</a>
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<p>In a 29-year-old German woman with perinatal bradycardia and neonatal long QT syndrome (LQT15; <a href="/entry/616249">616249</a>), who later exhibited exercise-induced polymorphic ventricular ectopy, <a href="#8" class="mim-tip-reference" title="Makita, N., Yagihara, N., Crotti, L., Johnson, C. N., Beckmann, B.-M., Roh, M. S., Shigemizu, D., Lichtner, P., Ishikawa, T., Aiba, T., Homfray, T., Behr, E. R., and 27 others. <strong>Novel calmodulin mutations associated with congenital arrhythmia susceptibility.</strong> Circ. Cardiovasc. Genet. 7: 466-474, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24917665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24917665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24917665[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/10.1161/CIRCGENETICS.113.000459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24917665">Makita et al. (2014)</a> identified heterozygosity for a de novo c.396T-G transversion in the CALM2 gene, resulting in an asp132-to-glu (D132E) substitution at a conserved residue within the fourth EF-hand calcium-binding motif. The mutation was not found in her parents or in the dbSNP, 1000 Genomes Project, Exome Variant Server, or Helmholtz exome databases. Functional analysis demonstrated a 23-fold reduction in calcium-binding affinity with the D132E mutant compared to wildtype calmodulin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24917665" 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">rs398124649 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398124649;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=rs398124649" 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=rs398124649" 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=RCV000143840 OR RCV000162070" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000143840, RCV000162070" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000143840...</a>
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<p>In a Moroccan girl with long QT syndrome (LQT15; <a href="/entry/616249">616249</a>), who died at 11 years of age while dancing at a wedding, <a href="#8" class="mim-tip-reference" title="Makita, N., Yagihara, N., Crotti, L., Johnson, C. N., Beckmann, B.-M., Roh, M. S., Shigemizu, D., Lichtner, P., Ishikawa, T., Aiba, T., Homfray, T., Behr, E. R., and 27 others. <strong>Novel calmodulin mutations associated with congenital arrhythmia susceptibility.</strong> Circ. Cardiovasc. Genet. 7: 466-474, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24917665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24917665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24917665[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/10.1161/CIRCGENETICS.113.000459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24917665">Makita et al. (2014)</a> identified heterozygosity for a de novo c.407A-C transversion in the CALM2 gene, resulting in a gln136-to-pro (Q136P) substitution at a conserved residue in the fourth EF-hand calcium-binding motif. The mutation was not found in her unaffected parents, 4 unaffected sisters, or in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. Functional analysis demonstrated a 9-fold reduction in calcium-binding affinity with the Q136P mutant compared to wildtype calmodulin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24917665" 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">rs1573214163 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1573214163;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=rs1573214163" 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=rs1573214163" 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=RCV001003503 OR RCV002236070" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001003503, RCV002236070" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001003503...</a>
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<p>In a 14-year-old Indian girl with long QT syndrome (LQT15; <a href="/entry/616249">616249</a>), who was bradycardic with a QTc of 740 ms at birth, <a href="#2" class="mim-tip-reference" title="Boczek, N. J., Gomez-Hurtado, N., Ye, D., Calvert, M. L., Tester, D. J., Kryshtal, D. O., Hwang, H. S., Johnson, C. N., Chazin, W. J., Loporcaro, C. G., Shah, M., Papez, A. L., Lau, Y. R., Kanter, R., Knollmann, B. C., Ackerman, M. J. <strong>Spectrum and prevalence of CALM1-, CALM2-, and CALM3-encoded calmodulin variants in long QT syndrome and functional characterization of a novel long QT syndrome-associated calmodulin missense variant, E141G.</strong> Circ. Cardiovasc. Genet. 9: 136-146, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26969752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26969752</a>] [<a href="https://doi.org/10.1161/CIRCGENETICS.115.001323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26969752">Boczek et al. (2016)</a> identified heterozygosity for a c.389A-G transition (c.389A-G, NM_001743) in the CALM2 gene, resulting in an asp130-to-gly (D130G) substitution within the fourth EF hand. Family history was negative; parental DNA was unavailable for segregation analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26969752" 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>Using cardiomyocytes differentiated from induced pluripotent stem cells (iPSCs) from the 14-year-old Indian girl with LQTS who was originally reported by <a href="#2" class="mim-tip-reference" title="Boczek, N. J., Gomez-Hurtado, N., Ye, D., Calvert, M. L., Tester, D. J., Kryshtal, D. O., Hwang, H. S., Johnson, C. N., Chazin, W. J., Loporcaro, C. G., Shah, M., Papez, A. L., Lau, Y. R., Kanter, R., Knollmann, B. C., Ackerman, M. J. <strong>Spectrum and prevalence of CALM1-, CALM2-, and CALM3-encoded calmodulin variants in long QT syndrome and functional characterization of a novel long QT syndrome-associated calmodulin missense variant, E141G.</strong> Circ. Cardiovasc. Genet. 9: 136-146, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26969752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26969752</a>] [<a href="https://doi.org/10.1161/CIRCGENETICS.115.001323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26969752">Boczek et al. (2016)</a>, <a href="#7" class="mim-tip-reference" title="Limpitikul, W. B., Dick, I. E., Tester, D. J., Boczek, N. J., Limphong, P., Yang, W., Choi, M. H., Babich, J., DiSilvestre, D., Kanter, R. J., Tomaselli, G. F., Ackerman, M. J., Yue, D. T. <strong>A precision medicine approach to the rescue of function on malignant calmodulinopathic long-QT syndrome.</strong> Circ. Res. 120: 39-48, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27765793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27765793</a>] [<a href="https://doi.org/10.1161/CIRCRESAHA.116.309283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27765793">Limpitikul et al. (2017)</a> characterized the D130G mutation in the CALM2 gene. The mutant cardiomyocytes exhibited dramatically longer action potentials than wildtype cells, and this was observed at multiple pacing frequencies, which the authors noted is a feature associated with increased arrhythmogenic risk. Monolayers of mutant cardiomyocytes showed calcium transient amplitudes that were more than 3 times larger than wildtype, with slower rise and decay kinetics. Whole-cell patch clamp recordings of individual cardiomyocytes revealed a profound attenuation in the kinetics and extent of Ca(2+)/calmodulin-dependent inactivation (CDI) of L-type Ca(2+) channels (LTCCs) in mutant cardiomyocytes compared to wildtype, without altering the voltage activation profile. Quantifying this result confirmed a significant decrease in CDI, and the reduction was significant even in the patient's background of 5 wildtype CALM alleles. <a href="#7" class="mim-tip-reference" title="Limpitikul, W. B., Dick, I. E., Tester, D. J., Boczek, N. J., Limphong, P., Yang, W., Choi, M. H., Babich, J., DiSilvestre, D., Kanter, R. J., Tomaselli, G. F., Ackerman, M. J., Yue, D. T. <strong>A precision medicine approach to the rescue of function on malignant calmodulinopathic long-QT syndrome.</strong> Circ. Res. 120: 39-48, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27765793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27765793</a>] [<a href="https://doi.org/10.1161/CIRCRESAHA.116.309283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27765793">Limpitikul et al. (2017)</a> suggested that the loss of LTCC CDI is a significant underlying mechanism causing arrhythmogenesis in patients with calmodulin-associated LQTS. Using a CRISPR interference short guide RNA to selectively reduce expression of both mutant and wildtype CALM2, without appreciable alteration of either CALM1 or CALM3, <a href="#7" class="mim-tip-reference" title="Limpitikul, W. B., Dick, I. E., Tester, D. J., Boczek, N. J., Limphong, P., Yang, W., Choi, M. H., Babich, J., DiSilvestre, D., Kanter, R. J., Tomaselli, G. F., Ackerman, M. J., Yue, D. T. <strong>A precision medicine approach to the rescue of function on malignant calmodulinopathic long-QT syndrome.</strong> Circ. Res. 120: 39-48, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27765793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27765793</a>] [<a href="https://doi.org/10.1161/CIRCRESAHA.116.309283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27765793">Limpitikul et al. (2017)</a> demonstrated normalization of the cardiac action potential duration (APD) and the LTCC CDI mechanism in the patient's iPSC-generated cardiomyocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27765793+26969752" 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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Berchtold, M. W., Egli, R., Rhyner, J. A., Hameister, H., Strehler, E. E.
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<strong>Localization of the human bona fide calmodulin genes CALM1, CALM2, and CALM3 to chromosomes 14q24-q31, 2p21.1-p21.3, and 19q13.2-q13.3.</strong>
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Genomics 16: 461-465, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8314583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8314583</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8314583" 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/10.1006/geno.1993.1211" target="_blank">Full Text</a>]
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Boczek, N. J., Gomez-Hurtado, N., Ye, D., Calvert, M. L., Tester, D. J., Kryshtal, D. O., Hwang, H. S., Johnson, C. N., Chazin, W. J., Loporcaro, C. G., Shah, M., Papez, A. L., Lau, Y. R., Kanter, R., Knollmann, B. C., Ackerman, M. J.
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<strong>Spectrum and prevalence of CALM1-, CALM2-, and CALM3-encoded calmodulin variants in long QT syndrome and functional characterization of a novel long QT syndrome-associated calmodulin missense variant, E141G.</strong>
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Circ. Cardiovasc. Genet. 9: 136-146, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26969752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26969752</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26969752" 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/10.1161/CIRCGENETICS.115.001323" target="_blank">Full Text</a>]
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Crotti, L., Johnson, C. N., Graf, E., De Ferrari, G. M., Cuneo, B. F., Ovadia, M., Papagiannis, J., Feldkamp, M. D., Rathi, S. G., Kunic, J. D., Pedrazzini, M., Wieland, T., and 11 others.
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<strong>Calmodulin mutations associated with recurrent cardiac arrest in infants.</strong>
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Circulation 127: 1009-1017, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23388215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23388215</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23388215[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=23388215" 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/10.1161/CIRCULATIONAHA.112.001216" target="_blank">Full Text</a>]
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Crotti, L., Spazzolini, C., Tester, D. J., Ghidoni, A., Baruteau, A.-E., Beckmann, B.-M., Behr, E. R., Bennet, J. S., Bezzina, C. R., Bhuiyan, Z. A., Celiker, A., Cerrone, M., and 29 others.
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<strong>Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry.</strong>
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Europ. Heart J. 40: 2964-2975, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31170290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31170290</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31170290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<div class="">
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<p class="mim-text-font">
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Fischer, R., Koller, M., Flura, M., Mathews, S., Strehler-Page, M.-A., Krebs, J., Penniston, J. T., Carafoli, E., Strehler, E. E.
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|
<strong>Multiple divergent mRNAs code for a single human calmodulin.</strong>
|
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J. Biol. Chem. 263: 17055-17062, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3182832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3182832</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3182832" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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<a id="6" class="mim-anchor"></a>
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<a id="Gomez-Hurtado2016" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Gomez-Hurtado, N., Boczek, N. J., Kryshtal, D. O., Johnson, C. N., Sun, J., Nitu, F. R., Cornea, R. L., Chazin, W. J., Calvert, M. L., Tester, D. J., Ackerman, M. J., Knollmann, B. C.
|
|
<strong>Novel CPVT-associated calmodulin mutation in CALM3 (CALM3-A103V) activates arrhythmogenic Ca waves and sparks.</strong>
|
|
Circ. Arrhythm. Electrophysiol. 9: e004161, 2016. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27516456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27516456</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27516456" 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/10.1161/CIRCEP.116.004161" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Limpitikul2017" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Limpitikul, W. B., Dick, I. E., Tester, D. J., Boczek, N. J., Limphong, P., Yang, W., Choi, M. H., Babich, J., DiSilvestre, D., Kanter, R. J., Tomaselli, G. F., Ackerman, M. J., Yue, D. T.
|
|
<strong>A precision medicine approach to the rescue of function on malignant calmodulinopathic long-QT syndrome.</strong>
|
|
Circ. Res. 120: 39-48, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27765793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27765793</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27765793" 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/10.1161/CIRCRESAHA.116.309283" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Makita2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Makita, N., Yagihara, N., Crotti, L., Johnson, C. N., Beckmann, B.-M., Roh, M. S., Shigemizu, D., Lichtner, P., Ishikawa, T., Aiba, T., Homfray, T., Behr, E. R., and 27 others.
|
|
<strong>Novel calmodulin mutations associated with congenital arrhythmia susceptibility.</strong>
|
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Circ. Cardiovasc. Genet. 7: 466-474, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24917665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24917665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24917665[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=24917665" 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/10.1161/CIRCGENETICS.113.000459" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="McPherson1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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McPherson, J. D., Hickie, R. A., Wasmuth, J. J., Meyskens, F. L., Perham, R. N., Strehler, E. E., Graham, M. T.
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|
<strong>Chromosomal localization of multiple genes encoding calmodulin. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 58: 1951 only, 1991.
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="SenGupta1987" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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SenGupta, B., Friedberg, F., Detera-Wadleigh, S. D.
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<strong>Molecular analysis of human and rat calmodulin complementary DNA clones: evidence for additional active genes in these species.</strong>
|
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J. Biol. Chem. 262: 16663-16670, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2445749/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2445749</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2445749" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Toutenhoofd1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Toutenhoofd, S. L., Foletti, D., Wicki, R., Rhyner, J. A., Garcia, F., Tolon, R., Strehler, E. E.
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<strong>Characterization of the human CALM2 calmodulin gene and comparison of the transcriptional activity of CALM1, CALM2, and CALM3.</strong>
|
|
Cell Calcium 23: 323-338, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9681195/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9681195</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9681195" 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/s0143-4160(98)90028-8" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 02/26/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 02/21/2020<br>Marla J. F. O'Neill - updated : 2/27/2015<br>Patricia A. Hartz - updated : 11/18/2002
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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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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 3/8/1992
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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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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 02/26/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 02/21/2020<br>alopez : 02/21/2020<br>carol : 01/28/2020<br>carol : 04/14/2017<br>alopez : 03/02/2015<br>mcolton : 2/27/2015<br>mgross : 11/18/2002<br>terry : 10/31/1996<br>carol : 5/26/1993<br>supermim : 3/16/1992<br>carol : 3/8/1992
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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> 114182
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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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CALMODULIN 2; CALM2
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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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PHKD2
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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: CALM2</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: 2p21
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:47,160,082-47,176,936 </span>
|
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</em>
|
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</strong>
|
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<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
|
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
|
2p21
|
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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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|
Long QT syndrome 15
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
616249
|
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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 dominant
|
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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">
|
|
<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>Calmodulin is an essential calcium-sensing, signal-transducing protein. Three calmodulin genes, CALM1 (114180), CALM2, and CALM3 (114183), have unique nucleotide sequences but encode identical 149-amino acid calmodulin proteins with 4 EF-hand calcium-binding loops. Calcium-induced activation of calmodulin regulates many calcium-dependent processes and modulates the function of cardiac ion channels, including CaV1.2 (CACNA1C; 114205), NaV1.5 (SCN5A; 600163), and the ryanodine receptor (RYR2; 180902) (summary by Boczek et al., 2016). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Cloning and Expression</strong>
|
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>SenGupta et al. (1987) first identified and cloned the second calmodulin gene. Fischer et al. (1988) noted that, although the CALM1, CALM2, and CALM3 proteins are identical, at the nucleotide level they share only about 80% identity within their coding regions, and they contain no significant homology within their noncoding regions. </p><p>Using a sequence from CALM3 as probe, Toutenhoofd et al. (1998) cloned CALM2 from a small intestine mucosa cDNA library. Northern blot analysis revealed a major 1.4-kb transcript in all tissues tested, with highest expression in brain. High levels of expression were also found in heart, placenta, lung, liver, skeletal muscle, and kidney, with lowest levels found in pancreas. </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>Gene Structure</strong>
|
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</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Toutenhoofd et al. (1998) determined that the CALM2 gene contains 6 exons and spans more than 16 kb. Within the 5-prime flanking region, CALM2 contains a TATA-like sequence, a far upstream CCAAT box, several AP1 (165160)-, AP2 (see 107580)-, and CRE (see 123811)-binding sites, and a repeated AGGGA motif that is found in other CALM genes. </p>
|
|
</span>
|
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<div>
|
|
<br />
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
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</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>McPherson et al. (1991) tentatively assigned the CALM2 gene to chromosome 10 by study of somatic cell hybrids. However, by PCR-based amplification of CALM2-specific sequences using DNA from human/hamster cell hybrids as template, Berchtold et al. (1993) found that the CALM2 gene is located on chromosome 2. They regionalized the gene to 2p21.3-p21.1 by in situ hybridization. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Long QT Syndrome 15</em></strong></p><p>
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In a Hispanic girl with markedly prolonged QTc intervals and multiple episodes of ventricular fibrillation (LQT15; 616249), Crotti et al. (2013) performed exome sequencing and identified a heterozygous de novo missense mutation in the CALM2 gene (D96V; 114182.0001). </p><p>In 5 unrelated patients of varying ancestry with long QT syndrome, Makita et al. (2014) identified heterozygosity for 5 different de novo missense mutations in the CALM2 gene (114182.0002-114182.0006). Functional analysis demonstrated significant reductions in calcium-binding affinity with the variants compared to wildtype calmodulin. </p><p>Boczek et al. (2016) performed whole-exome sequencing in 38 unrelated LQTS patients who were negative for mutation in 14 known LQTS-associated genes and identified a 14-year-old Indian girl and a 7-year-old white boy who were heterozygous for 2 different missense mutations at the same codon in the CALM2 gene, D130G (114182.0007) and D130V, respectively. </p><p><strong><em>Reviews</em></strong></p><p>
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|
Crotti et al. (2019) reviewed 74 patients, from the International Calmodulinopathy Registry and from the published literature, who had mutations in the CALM1 (114180), CALM2, or CALM3 (114183) genes (36, 23, and 15 patients, respectively) and who did not have clinically relevant pathogenic variants in other arrhythmia-susceptibility genes. Sixty-four (86.5%) of the patients were symptomatic, and the 10-year cumulative mortality was 27%. The 2 prevalent phenotypes were LQTS (49%) and CPVT (28%); other diagnoses included idiopathic ventricular fibrillation (10%), sudden unexplained death (5%), and overlapping features of LQTS/CPVT (4%). The majority of variants (80%) affected amino acid residues on the EF-hand Ca(2+)-binding loops III and IV, and almost 90% of them affected 1 of the 4 residues principally involved in Ca(2+) binding (Asp, Asp, Asp/Asn, and Glu, at positions 1, 3, 5, and 12, respectively, from the beginning of each 12-residue loop). Three residues appeared to be relative hotspots, with N98S, D130G, and F142L identified in 10, 5, and 4 families, respectively. The authors noted that LQTS-associated calmodulin variants, located primarily in EF hands III and IV, show a strong dominant-negative reduction in Ca(2+)-dependent inactivation of the L-type Ca(2+) channel Ca(v)1.2 (CACNA1C; 114205), which results in repolarization delay However, the major effect of CPVT-associated variants, mostly located in either EF hand III or in the inter-EF hand I-II linker, appears to be a higher binding affinity for RyR2 (180902), promoting its open conformation and increasing the frequency of Ca(2+) waves. The authors added that no gene-specific phenotypic correlations could be made since mutations in all 3 calmodulin genes may give rise to different phenotypes. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>7 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 LONG QT SYNDROME 15</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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CALM2, ASP96VAL
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<br />
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SNP: rs730882254,
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ClinVar: RCV000162065, RCV001547926, RCV001850284
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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 a Hispanic girl with markedly prolonged QTc intervals and multiple episodes of ventricular fibrillation (LQT15; 616249), Crotti et al. (2013) identified heterozygosity for a de novo A-T transversion in the CALM2 gene, resulting in an asp96-to-val (D96V) substitution at a highly conserved residue in the EF-hand domain III. The mutation was not found in 92 Hispanic American controls or in the dbSNP (build 130), 1000 Genomes Project, Exome Variant Server, or Helmholtz exome databases. Functional analysis demonstrated a 13-fold reduction in calcium-binding affinity with the mutant compared to wildtype calmodulin. </p><p>Gomez-Hurtado et al. (2016) studied the CALM2 D96V mutation in permeabilized mouse ventricular myocytes and observed significantly increased L-type calcium channel inactivation time with the mutant compared to wildtype calmodulin. In addition, the D96V mutation dramatically increased the action potential duration at both 50% and 90% of repolarization. Early after-depolarizations were observed in 36% of cardiomyocytes dialyzed with the D96V mutant, which the authors noted was consistent with the clinical phenotype of LQTS. </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 LONG QT SYNDROME 15</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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CALM2, ASP134HIS
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<br />
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SNP: rs398124650,
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ClinVar: RCV000143839, RCV000162066
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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 a 16-year-old Japanese girl who had fetal bradycardia and episodes of syncope in early childhood and was found to have marked QTc prolongation on electrocardiography (LQT15; 616249), Makita et al. (2014) identified heterozygosity for a de novo c.400G-C transversion in exon 5 of the CALM2 gene, resulting in an asp134-to-his (D134H) substitution at a conserved residue within the fourth EF-hand calcium-binding motif in the C-terminal domain. The mutation was not found in her unaffected parents, 2 unaffected brothers, or in the dbSNP, 1000 Genomes Project, Exome Variant Server, RIKEN, or Human Genetic Variation Browser databases. Functional analysis demonstrated a 13-fold reduction in calcium-binding affinity with the D134H mutant compared to wildtype calmodulin. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0003 LONG QT SYNDROME 15</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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CALM2, ASN98SER
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<br />
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SNP: rs398124647,
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ClinVar: RCV000143836, RCV000162067, RCV003318349
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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 12-year-old Japanese boy with episodes of syncope on exertion and QTc prolongation on electrocardiography (LQT15; 616249), Makita et al. (2014) identified heterozygosity for a de novo c.293A-G transition in exon 5 of the CALM2 gene, resulting in an asn98-to-ser (N98S) substitution at a conserved residue within the third EF-hand calcium-binding motif in the C-terminal domain. The mutation was not found in his unaffected parents or brother. </p><p>Gomez-Hurtado et al. (2016) studied the CALM2 N98S mutation in permeabilized mouse ventricular myocytes and observed significantly increased spark frequency and reduced sarcoplasmic reticulum Ca(2+) content with the mutant compared to wildtype calmodulin. The cardiomyocytes also showed increased spontaneous Ca(2+) release in the form of regular propagated Ca(2+) waves with the mutant compared to wildtype calmodulin, and the mutant demonstrated a dominant effect, with significantly higher Ca(2+) wave frequencies even in the presence of 3-fold excess of wildtype calmodulin. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 LONG QT SYNDROME 15</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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CALM2, ASN98ILE
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<br />
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SNP: rs398124647,
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|
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ClinVar: RCV000143837, RCV000162068
|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2.5-year-old English boy who had cardiac arrest due to ventricular fibrillation at 17 months of age, and in whom electrocardiography showed bradycardia and a prolonged QTc interval (LQT15; 616249), Makita et al. (2014) identified heterozygosity for a de novo c.293A-T transversion in exon 5 of the CALM2 gene, resulting in an asn98-to-ile (N98I) substitution at a conserved residue within the third EF-hand calcium-binding motif in the C-terminal domain. The mutation was not present in his unaffected parents. Functional analysis demonstrated a 7-fold reduction in calcium-binding affinity with the N98I mutant compared to wildtype calmodulin. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 LONG QT SYNDROME 15</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CALM2, ASP132GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398124648,
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|
|
|
|
|
|
|
ClinVar: RCV000143838, RCV000162069
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 29-year-old German woman with perinatal bradycardia and neonatal long QT syndrome (LQT15; 616249), who later exhibited exercise-induced polymorphic ventricular ectopy, Makita et al. (2014) identified heterozygosity for a de novo c.396T-G transversion in the CALM2 gene, resulting in an asp132-to-glu (D132E) substitution at a conserved residue within the fourth EF-hand calcium-binding motif. The mutation was not found in her parents or in the dbSNP, 1000 Genomes Project, Exome Variant Server, or Helmholtz exome databases. Functional analysis demonstrated a 23-fold reduction in calcium-binding affinity with the D132E mutant compared to wildtype calmodulin. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
|
</div>
|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 LONG QT SYNDROME 15</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CALM2, GLN136PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398124649,
|
|
|
|
|
|
|
|
ClinVar: RCV000143840, RCV000162070
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Moroccan girl with long QT syndrome (LQT15; 616249), who died at 11 years of age while dancing at a wedding, Makita et al. (2014) identified heterozygosity for a de novo c.407A-C transversion in the CALM2 gene, resulting in a gln136-to-pro (Q136P) substitution at a conserved residue in the fourth EF-hand calcium-binding motif. The mutation was not found in her unaffected parents, 4 unaffected sisters, or in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. Functional analysis demonstrated a 9-fold reduction in calcium-binding affinity with the Q136P mutant compared to wildtype calmodulin. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 LONG QT SYNDROME 15</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CALM2, ASP130GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1573214163,
|
|
|
|
|
|
|
|
ClinVar: RCV001003503, RCV002236070
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 14-year-old Indian girl with long QT syndrome (LQT15; 616249), who was bradycardic with a QTc of 740 ms at birth, Boczek et al. (2016) identified heterozygosity for a c.389A-G transition (c.389A-G, NM_001743) in the CALM2 gene, resulting in an asp130-to-gly (D130G) substitution within the fourth EF hand. Family history was negative; parental DNA was unavailable for segregation analysis. </p><p>Using cardiomyocytes differentiated from induced pluripotent stem cells (iPSCs) from the 14-year-old Indian girl with LQTS who was originally reported by Boczek et al. (2016), Limpitikul et al. (2017) characterized the D130G mutation in the CALM2 gene. The mutant cardiomyocytes exhibited dramatically longer action potentials than wildtype cells, and this was observed at multiple pacing frequencies, which the authors noted is a feature associated with increased arrhythmogenic risk. Monolayers of mutant cardiomyocytes showed calcium transient amplitudes that were more than 3 times larger than wildtype, with slower rise and decay kinetics. Whole-cell patch clamp recordings of individual cardiomyocytes revealed a profound attenuation in the kinetics and extent of Ca(2+)/calmodulin-dependent inactivation (CDI) of L-type Ca(2+) channels (LTCCs) in mutant cardiomyocytes compared to wildtype, without altering the voltage activation profile. Quantifying this result confirmed a significant decrease in CDI, and the reduction was significant even in the patient's background of 5 wildtype CALM alleles. Limpitikul et al. (2017) suggested that the loss of LTCC CDI is a significant underlying mechanism causing arrhythmogenesis in patients with calmodulin-associated LQTS. Using a CRISPR interference short guide RNA to selectively reduce expression of both mutant and wildtype CALM2, without appreciable alteration of either CALM1 or CALM3, Limpitikul et al. (2017) demonstrated normalization of the cardiac action potential duration (APD) and the LTCC CDI mechanism in the patient's iPSC-generated cardiomyocytes. </p>
|
|
</span>
|
|
</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>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
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<p />
|
|
</div>
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<div>
|
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<ol>
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<li>
|
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<p class="mim-text-font">
|
|
Berchtold, M. W., Egli, R., Rhyner, J. A., Hameister, H., Strehler, E. E.
|
|
<strong>Localization of the human bona fide calmodulin genes CALM1, CALM2, and CALM3 to chromosomes 14q24-q31, 2p21.1-p21.3, and 19q13.2-q13.3.</strong>
|
|
Genomics 16: 461-465, 1993.
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|
|
[PubMed: 8314583]
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[Full Text: https://doi.org/10.1006/geno.1993.1211]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Boczek, N. J., Gomez-Hurtado, N., Ye, D., Calvert, M. L., Tester, D. J., Kryshtal, D. O., Hwang, H. S., Johnson, C. N., Chazin, W. J., Loporcaro, C. G., Shah, M., Papez, A. L., Lau, Y. R., Kanter, R., Knollmann, B. C., Ackerman, M. J.
|
|
<strong>Spectrum and prevalence of CALM1-, CALM2-, and CALM3-encoded calmodulin variants in long QT syndrome and functional characterization of a novel long QT syndrome-associated calmodulin missense variant, E141G.</strong>
|
|
Circ. Cardiovasc. Genet. 9: 136-146, 2016.
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|
[PubMed: 26969752]
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[Full Text: https://doi.org/10.1161/CIRCGENETICS.115.001323]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Crotti, L., Johnson, C. N., Graf, E., De Ferrari, G. M., Cuneo, B. F., Ovadia, M., Papagiannis, J., Feldkamp, M. D., Rathi, S. G., Kunic, J. D., Pedrazzini, M., Wieland, T., and 11 others.
|
|
<strong>Calmodulin mutations associated with recurrent cardiac arrest in infants.</strong>
|
|
Circulation 127: 1009-1017, 2013.
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[PubMed: 23388215]
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[Full Text: https://doi.org/10.1161/CIRCULATIONAHA.112.001216]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Crotti, L., Spazzolini, C., Tester, D. J., Ghidoni, A., Baruteau, A.-E., Beckmann, B.-M., Behr, E. R., Bennet, J. S., Bezzina, C. R., Bhuiyan, Z. A., Celiker, A., Cerrone, M., and 29 others.
|
|
<strong>Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry.</strong>
|
|
Europ. Heart J. 40: 2964-2975, 2019.
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[PubMed: 31170290]
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[Full Text: https://doi.org/10.1093/eurheartj/ehz311]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Fischer, R., Koller, M., Flura, M., Mathews, S., Strehler-Page, M.-A., Krebs, J., Penniston, J. T., Carafoli, E., Strehler, E. E.
|
|
<strong>Multiple divergent mRNAs code for a single human calmodulin.</strong>
|
|
J. Biol. Chem. 263: 17055-17062, 1988.
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[PubMed: 3182832]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Gomez-Hurtado, N., Boczek, N. J., Kryshtal, D. O., Johnson, C. N., Sun, J., Nitu, F. R., Cornea, R. L., Chazin, W. J., Calvert, M. L., Tester, D. J., Ackerman, M. J., Knollmann, B. C.
|
|
<strong>Novel CPVT-associated calmodulin mutation in CALM3 (CALM3-A103V) activates arrhythmogenic Ca waves and sparks.</strong>
|
|
Circ. Arrhythm. Electrophysiol. 9: e004161, 2016. Note: Electronic Article.
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[PubMed: 27516456]
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[Full Text: https://doi.org/10.1161/CIRCEP.116.004161]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Limpitikul, W. B., Dick, I. E., Tester, D. J., Boczek, N. J., Limphong, P., Yang, W., Choi, M. H., Babich, J., DiSilvestre, D., Kanter, R. J., Tomaselli, G. F., Ackerman, M. J., Yue, D. T.
|
|
<strong>A precision medicine approach to the rescue of function on malignant calmodulinopathic long-QT syndrome.</strong>
|
|
Circ. Res. 120: 39-48, 2017.
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|
[PubMed: 27765793]
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[Full Text: https://doi.org/10.1161/CIRCRESAHA.116.309283]
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</p>
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</li>
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Makita, N., Yagihara, N., Crotti, L., Johnson, C. N., Beckmann, B.-M., Roh, M. S., Shigemizu, D., Lichtner, P., Ishikawa, T., Aiba, T., Homfray, T., Behr, E. R., and 27 others.
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<strong>Novel calmodulin mutations associated with congenital arrhythmia susceptibility.</strong>
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Circ. Cardiovasc. Genet. 7: 466-474, 2014.
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[PubMed: 24917665]
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[Full Text: https://doi.org/10.1161/CIRCGENETICS.113.000459]
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McPherson, J. D., Hickie, R. A., Wasmuth, J. J., Meyskens, F. L., Perham, R. N., Strehler, E. E., Graham, M. T.
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<strong>Chromosomal localization of multiple genes encoding calmodulin. (Abstract)</strong>
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Cytogenet. Cell Genet. 58: 1951 only, 1991.
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SenGupta, B., Friedberg, F., Detera-Wadleigh, S. D.
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<strong>Molecular analysis of human and rat calmodulin complementary DNA clones: evidence for additional active genes in these species.</strong>
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J. Biol. Chem. 262: 16663-16670, 1987.
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[PubMed: 2445749]
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Toutenhoofd, S. L., Foletti, D., Wicki, R., Rhyner, J. A., Garcia, F., Tolon, R., Strehler, E. E.
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<strong>Characterization of the human CALM2 calmodulin gene and comparison of the transcriptional activity of CALM1, CALM2, and CALM3.</strong>
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Cell Calcium 23: 323-338, 1998.
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[PubMed: 9681195]
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[Full Text: https://doi.org/10.1016/s0143-4160(98)90028-8]
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Marla J. F. O'Neill - updated : 02/26/2020<br>Marla J. F. O'Neill - updated : 02/21/2020<br>Marla J. F. O'Neill - updated : 2/27/2015<br>Patricia A. Hartz - updated : 11/18/2002
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Victor A. McKusick : 3/8/1992
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