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Entry
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- *114180 - CALMODULIN 1; CALM1
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*114180</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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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="#biochemicalFeatures">Biochemical Features</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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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#history">History</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/114180">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>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<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-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000198668;t=ENST00000356978" 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=801" 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=114180" 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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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000198668;t=ENST00000356978" 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_001363669,NM_001363670,NM_006888" 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_006888" 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=114180" 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=00241&isoform_id=00241_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/CALM1" 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/179810,531827,5542035,5901912,12653369,14044088,14250335,15080116,30582475,37779144,119601833,119601834,158260897,1191692486,1393170119,1393428084" 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/P0DP23" 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=801" 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=ENSG00000198668;t=ENST00000356978" 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=CALM1" 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=CALM1" 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+801" 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/CALM1" 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:801" 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/801" 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=chr14&hgg_gene=ENST00000356978.9&hgg_start=90396502&hgg_end=90408268&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 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:1442" 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:1442" 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=114180[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=114180[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/ENSG00000198668" 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=CALM1" 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=CALM1" 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=CALM1" 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=CALM1&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/PA26035" 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:1442" 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:88251" 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/CALM1#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:88251" 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/801/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=801" 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-030131-8308" 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">
|
|
<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:801" 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=CALM1&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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114180
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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 1; CALM1
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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>
|
|
<span class="mim-font">
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PHOSPHORYLASE KINASE, DELTA SUBUNIT; PHKD
|
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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=CALM1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CALM1</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">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/14/455?start=-3&limit=10&highlight=455">14q32.11</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:90396502-90408268&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'})">14:90,396,502-90,408,268</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
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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">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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|
Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=616247,614916" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
|
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</span>
|
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</th>
|
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/14/455?start=-3&limit=10&highlight=455">
|
|
14q32.11
|
|
</a>
|
|
</span>
|
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</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Long QT syndrome 14
|
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|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616247"> 616247 </a>
|
|
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<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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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Ventricular tachycardia, catecholaminergic polymorphic, 4
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/614916"> 614916 </a>
|
|
|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<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>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
|
</span>
|
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</td>
|
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</tr>
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</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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<p>Calmodulin is an essential calcium-sensing, signal-transducing protein. Three calmodulin genes, CALM1, CALM2 (<a href="/entry/114182">114182</a>), 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="#4" 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://www.ncbi.nlm.nih.gov/pmc/?term=26969752[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.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>Until the studies of <a href="#28" 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>, only 1 human calmodulin cDNA had been reported. These authors found evidence of a second actively transcribed calmodulin gene in man. Calmodulin is the delta subunit of phosphorylase kinase, which has 3 other types of subunits. Although only 1 form of calmodulin has been found in humans, 3 distinct human cDNAs have been isolated that encode the identical polypeptide (<a href="#13" class="mim-tip-reference" title="Koller, M., Schnyder, B., Strehler, E. E. <strong>Structural organization of the human CaMIII calmodulin gene.</strong> Biochim. Biophys. Acta 1087: 180-189, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2223880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2223880</a>] [<a href="https://doi.org/10.1016/0167-4781(90)90203-e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2223880">Koller et al., 1990</a>; <a href="#22" class="mim-tip-reference" title="Pegues, J. C., Friedberg, F. <strong>Multiple mRNAs encoding human calmodulin.</strong> Biochem. Biophys. Res. Commun. 172: 1145-1149, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2244899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2244899</a>] [<a href="https://doi.org/10.1016/0006-291x(90)91567-c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2244899">Pegues and Friedberg, 1990</a>). The existence of 3 expressible genes for calmodulin may indicate that one is a housekeeping gene and that the additional copies are differentially regulated to modulate calmodulin function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2223880+2244899+2445749" 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="#23" class="mim-tip-reference" title="Rhyner, J. A., Ottiger, M., Wicki, R., Greenwood, T. M., Strehler, E. E. <strong>Structure of the human CALM1 calmodulin gene and identification of two CALM1-related pseudogenes CALM1P1 and CALM1P2.</strong> Europ. J. Biochem. 225: 71-82, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7925473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7925473</a>] [<a href="https://doi.org/10.1111/j.1432-1033.1994.00071.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7925473">Rhyner et al. (1994)</a> detected expression of CALM1 in all human tissues tested, although at varying levels. They identified 2 different CALM1-related pseudogenes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7925473" 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="#29" 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> found that all 3 CALM genes were expressed in human teratocarcinoma cells. CALM1 was expressed as a major 1.7-kb transcript and a minor 4.1-kb transcript. CALM1 was at least 5-fold less actively transcribed than CALM3 (<a href="/entry/114183">114183</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'})"><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>To determine how calcium/calmodulin activates calcium/calmodulin-dependent protein kinase I (CAMK1; <a href="/entry/604998">604998</a>), <a href="#5" class="mim-tip-reference" title="Chin, D., Winkler, K. E., Means, A. R. <strong>Characterization of substrate phosphorylation and use of calmodulin mutants to address implications from the enzyme crystal structure of calmodulin-dependent protein kinase I.</strong> J. Biol. Chem. 272: 31235-31240, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9395448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9395448</a>] [<a href="https://doi.org/10.1074/jbc.272.50.31235" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9395448">Chin et al. (1997)</a> characterized CAMK1 activation by calmodulin mutants with substitutions at hydrophobic residues. They found that CAMK1 activity is dependent on met124 within the C-terminal domain of calmodulin as well as on N-terminal hydrophobic residues of calmodulin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9395448" 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="#14" class="mim-tip-reference" title="Kretsinger, R. H., Rudnick, S. E., Weissman, L. J. <strong>Crystal structure of calmodulin.</strong> J. Inorg. Biochem. 28: 289-302, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3806094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3806094</a>] [<a href="https://doi.org/10.1016/0162-0134(86)80093-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3806094">Kretsinger et al. (1986)</a> described the crystal structure of calmodulin to 3.6-angstrom resolution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3806094" 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="#25" class="mim-tip-reference" title="Schumacher, M. A., Rivard, A. F., Bachinger, H. P., Adelman, J. P. <strong>Structure of the gating domain of a Ca(2+)-activated K+ channel complexed with Ca(2+)/calmodulin.</strong> Nature 410: 1120-1124, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11323678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11323678</a>] [<a href="https://doi.org/10.1038/35074145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11323678">Schumacher et al. (2001)</a> determined the crystal structure of calmodulin bound to KCNN2 (<a href="/entry/605879">605879</a>). The calmodulin-binding domain forms an elongated dimer with a calmodulin molecule bound at each end; each calmodulin wraps around 3 alpha-helices, 2 from 1 calmodulin-binding domain subunit and 1 from the other. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11323678" 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>Edema factor, the exotoxin of the anthrax bacillus, is transported into host cells by an anthrax-derived transporter, protective antigen. Together with lethal factor (see <a href="/entry/603060">603060</a>), edema factor contributes significantly to both cutaneous and systemic anthrax and is an adenylyl cyclase activated by CALM1. <a href="#9" class="mim-tip-reference" title="Drum, C. L., Yan, S.-Z., Bard, J., Shen, Y.-Q., Lu, D., Soelaiman, S., Grabarek, Z., Bohm, A., Tang, W.-J. <strong>Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin.</strong> Nature 415: 396-402, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11807546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11807546</a>] [<a href="https://doi.org/10.1038/415396a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11807546">Drum et al. (2002)</a> described the crystal structures of edema factor alone and edema factor with CALM1 and 3-prime-deoxy-ATP. On calmodulin binding, an edema factor helical domain of 15 kD undergoes a 15-angstrom translation and a 30-degree rotation away from the edema factor catalytic core, which stabilizes a disordered loop and leads to enzyme activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11807546" 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="#23" class="mim-tip-reference" title="Rhyner, J. A., Ottiger, M., Wicki, R., Greenwood, T. M., Strehler, E. E. <strong>Structure of the human CALM1 calmodulin gene and identification of two CALM1-related pseudogenes CALM1P1 and CALM1P2.</strong> Europ. J. Biochem. 225: 71-82, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7925473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7925473</a>] [<a href="https://doi.org/10.1111/j.1432-1033.1994.00071.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7925473">Rhyner et al. (1994)</a> found that the CALM1 gene contains 6 exons spread over about 10 kb of genomic DNA. The exon-intron structure was identical to that of CALM3. A cluster of transcription-start sites was identified 200 bp upstream of the ATG translation-start codon, and several putative regulatory elements were found in the 5-prime flanking region, as well as in intron 1. A short CAG trinucleotide repeat region was identified in the 5-prime untranslated region of the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7925473" 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="#29" 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 of the 3 CALM genes, only CALM1 contains a canonical TATA box. Like CALM3, the 5-prime region of CALM1 is highly GC rich. <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="#18" 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> used a panel of human/rodent somatic cell hybrids to demonstrate that the cDNA probe for CALM1 was localized to chromosome 14 with cross-hybridization evident on chromosome 7 and very weak on the X chromosome. The assignments to chromosomes 14 and 7 confirmed an earlier report by <a href="#24" class="mim-tip-reference" title="Scambler, P. J., McPherson, M. A., Bates, G., Bradbury, N. A., Dormer, R. L., Williamson, R. <strong>Biochemical and genetic exclusion of calmodulin as the site of the basic defect in cystic fibrosis.</strong> Hum. Genet. 76: 278-282, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2885258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2885258</a>] [<a href="https://doi.org/10.1007/BF00283623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2885258">Scambler et al. (1987)</a>. <a href="#18" 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 (<a href="/entry/114182">114182</a>) gene to chromosome 10, but the gene was subsequently shown to be on chromosome 2. They assigned the cDNA probe for CALM3 unequivocally to chromosome 19. There was no apparent cross-hybridization to other chromosomes. A calmodulin pseudogene is located on chromosome 17 (<a href="#27" class="mim-tip-reference" title="SenGupta, B., Detera-Wadleigh, S. D., McBride, O. W., Friedberg, F. <strong>A calmodulin pseudogene on human chromosome 17.</strong> Nucleic Acids Res. 17: 2868 only, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2717417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2717417</a>] [<a href="https://doi.org/10.1093/nar/17.7.2868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2717417">SenGupta et al., 1989</a>) and there are probably more on several other chromosomes. <a href="#3" 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> assigned the CALM1 gene to chromosome 14 by PCR-based amplification of CALM1-specific sequences using DNA from human/hamster cell hybrids as template. Regional sublocalization was performed by in situ hybridization using CALM1-specific DNA probes of intronic or flanking parts of the gene; the regional localization was found to be 14q24-q31. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8314583+2885258+2717417" 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>To understand the relationship between the number of calmodulin molecules regulating each L-type calcium channel (see <a href="/entry/114205">114205</a>) and the number of calmodulin molecules privy to the local calcium signal from each channel, <a href="#19" class="mim-tip-reference" title="Mori, M. X., Erickson, M. G., Yue, D. T. <strong>Functional stoichiometry and local enrichment of calmodulin interacting with Ca(2+) channels.</strong> Science 304: 432-435, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15087548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15087548</a>] [<a href="https://doi.org/10.1126/science.1093490" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15087548">Mori et al. (2004)</a> fused L-type calcium channels to single calmodulin molecules. These chimeric molecules revealed that a single calmodulin molecule directs L-type channel regulation. Similar fusion molecules were used to estimate the local calmodulin concentration near calcium channels. This estimate indicates marked enrichment of local calmodulin, as if a school of nearby calmodulins were poised to enhance the transduction of local calcium entry into diverse signaling pathways. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15087548" 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="#12" class="mim-tip-reference" title="Junge, H. J., Rhee, J.-S., Jahn, O., Varoqueaux, F., Spiess, J., Waxham, M. N., Rosenmund, C., Brose, N. <strong>Calmodulin and Munc13 form a Ca(2+) sensor/effector complex that controls short-term synaptic plasticity.</strong> Cell 118: 389-401, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15294163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15294163</a>] [<a href="https://doi.org/10.1016/j.cell.2004.06.029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15294163">Junge et al. (2004)</a> identified a conserved calmodulin-binding site in Munc13s (see <a href="/entry/605836">605836</a>), which are essential regulators of synaptic vesicle priming and synaptic efficacy. They showed that Ca(2+) sensor/effector complexes consisting of calmodulin and Munc13s regulate synaptic vesicle priming and synaptic efficacy in response to a residual Ca(2+) concentration signal and thus shape short-term plasticity characteristics during periods of sustained synaptic activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15294163" 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="#8" class="mim-tip-reference" title="Dick, I. E., Tadross, M. R., Liang, H., Tay, L. H., Yang, W., Yue, D. T. <strong>A modular switch for spatial Ca(2+) selectivity in the calmodulin regulation of Ca(v) channels.</strong> Nature 451: 830-834, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18235447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18235447</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18235447[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature06529" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18235447">Dick et al. (2008)</a> showed that the spatial calcium ion selectivity of N-lobe calmodulin regulation is not invariably global but can be switched by a novel calcium ion/calmodulin binding site within the amino terminus of channels (NSCaTE, for N-terminal spatial calcium ion transforming element). Native Ca(v)2.2 channels lack this element and show N-lobe regulation with a global selectivity. On the introduction of NSCaTE into these channels, spatial calcium ion selectivity transforms from a global to local profile. Given this effect, <a href="#8" class="mim-tip-reference" title="Dick, I. E., Tadross, M. R., Liang, H., Tay, L. H., Yang, W., Yue, D. T. <strong>A modular switch for spatial Ca(2+) selectivity in the calmodulin regulation of Ca(v) channels.</strong> Nature 451: 830-834, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18235447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18235447</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18235447[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature06529" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18235447">Dick et al. (2008)</a> examined Ca(v)1.2/Ca(v)1.3 channels, which naturally contain NSCaTE, and found that their N-lobe selectivity is indeed local. Disruption of this element produces a global selectivity, confirming the native function of NSCaTE. Thus, <a href="#8" class="mim-tip-reference" title="Dick, I. E., Tadross, M. R., Liang, H., Tay, L. H., Yang, W., Yue, D. T. <strong>A modular switch for spatial Ca(2+) selectivity in the calmodulin regulation of Ca(v) channels.</strong> Nature 451: 830-834, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18235447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18235447</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18235447[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature06529" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18235447">Dick et al. (2008)</a> concluded that differences in spatial selectivity between advanced Ca(v)1 and Ca(v)2 channel isoforms are explained by the presence or absence of NSCaTE. Beyond functional effects, the position of NSCaTE on the channel's amino terminus indicates that calmodulin can bridge the amino terminus and carboxy terminus of channels. Finally, the modularity of NSCaTE offers practical means for understanding the basis of global calcium ion selectivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18235447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Liu, X., Yang, P. S., Yang, W., Yue, D. T. <strong>Enzyme-inhibitor-like tuning of Ca(2+) channel connectivity with calmodulin.</strong> Nature 463: 968-972, 2010. Note: Erratum: Nature 464: 1390 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20139964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20139964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20139964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature08766" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20139964">Liu et al. (2010)</a> combined electrophysiology to characterize channel regulation with optical fluorescence resonance energy transfer (FRET) sensor determination of free-apoCaM concentration in live cells. This approach translates quantitative calmodulin biochemistry from the traditional test-tube context into the realm of functioning holochannels within intact cells. From this perspective, <a href="#15" class="mim-tip-reference" title="Liu, X., Yang, P. S., Yang, W., Yue, D. T. <strong>Enzyme-inhibitor-like tuning of Ca(2+) channel connectivity with calmodulin.</strong> Nature 463: 968-972, 2010. Note: Erratum: Nature 464: 1390 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20139964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20139964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20139964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature08766" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20139964">Liu et al. (2010)</a> found that long splice forms of Ca(V)1.3 (CACNA1D; <a href="/entry/114206">114206</a>) and Ca(V)1.4 (CACNA1F; <a href="/entry/300110">300110</a>) channels include a distal carboxy tail that resembles an enzyme competitive inhibitor that retunes channel affinity for apocalmodulin such that natural calmodulin variations affect the strength of Ca(2+) feedback modulation. Given the ubiquity of these channels, the connection between ambient calmodulin levels and Ca(2+) entry through channels is broadly significant for Ca(2+) homeostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20139964" 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>By knockout analysis in HEK293T cells, <a href="#11" class="mim-tip-reference" title="Haakonsen, D. L., Heider, M., Ingersoll, A. J., Vodehnal, K., Witus, S. R., Uenaka, T., Wernig, M., Rape, M. <strong>Stress response silencing by an E3 ligase mutated in neurodegeneration.</strong> Nature 626: 874-880, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38297121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38297121</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=38297121[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-023-06985-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38297121">Haakonsen et al. (2024)</a> demonstrated that the E3 ligase UBR4 (<a href="/entry/609890">609890</a>) was important when mitochondrial function was compromised. UBR4 bound KCMF1 (<a href="/entry/614719">614719</a>) and calmodulin to form an E3 ligase complex that sustained survival of cells undergoing mitochondrial import stress. The authors named the UBR4-KCMF1-calmodulin complex 'silencing factor of the integrated stress response,' or SIFI. SIFI targeted HRI (<a href="/entry/613635">613635</a>) and the cytosolic cleavage fragment of DELE1 (<a href="/entry/615741">615741</a>) (cDELE1), proteins that actively mediate the cellular response to mitochondrial import stress, to promote their ubiquitylation and degradation to silence the integrated stress response in cells. The N terminus of HRI contains 2 alpha helices that served as degrons, with each capable of mediating recognition by SIFI. Multiple motifs in cDELE1, including an N-terminal motif that was exposed after cleavage and a helix with similarity to HRI degrons, were recognized by SIFI. The helical HRI and cDELE1 degrons closely resembled mitochondrial presequences. Consequently, SIFI not only recognized and targeted HRI and cDELE1, but it also appeared to target other proteins containing a presequence, including unimported mitochondrial proteins that accumulated in the cytoplasm during import stress, for their ubiquitylation and degradation. Ubiquitylation of presequences depended on the calmodulin and KCMF1 subunits of SIFI. These mitochondrial presequences and cDELE1 and HRI degrons, which were similar to stress response degrons, were related bifunctional motifs that could be recognized by both the mitochondrial import machinery and SIFI. Consequently, these converging degrons were able to couple stress resolution to stress response silencing in cells. Further analysis revealed that HRI and DELE1 mediated stress response signaling without affecting mitochondrial protein import, and pharmacologic silencing of the stress response restored survival of UBR4- or KCMF1-knockout cells that failed to resolve mitochondrial stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38297121" 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><strong><em>Catecholaminergic Polymorphic Ventricular Tachycardia 4</em></strong></p><p>
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In a large 4-generation Swedish family with autosomal dominant catecholaminergic polymorphic ventricular tachycardia (CPVT4; <a href="/entry/614916">614916</a>), <a href="#21" class="mim-tip-reference" title="Nyegaard, M., Overgaard, M. T., Sondergaard, M. T., Vranas, M., Behr, E. R., Hildebrandt, L. L., Lund, J., Hedley, P. L., Camm, A. J., Wettrell, G., Fosdal, I., Christiansen, M., Borglum, A. D. <strong>Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death.</strong> Am. J. Hum. Genet. 91: 703-712, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23040497/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23040497</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23040497[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.08.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23040497">Nyegaard et al. (2012)</a> identified heterozygosity for a missense mutation in the CALM1 gene (N53I; <a href="#0001">114180.0001</a>) that segregated fully with disease in the family and was not found in 1,200 controls. A de novo missense mutation in CALM1 (N97S; <a href="#0002">114180.0002</a>) was subsequently identified in a 23-year-old Iraqi woman with a history of cardiac arrest at 4 years of age due to ventricular fibrillation while running. Both substitutions demonstrated compromised calcium binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23040497" 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>Long QT Syndrome 14</em></strong></p><p>
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In 3 children with markedly prolonged QTc intervals and life-threatening ventricular arrhythmias (LQT14; <a href="/entry/616247">616247</a>), <a href="#6" 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 de novo missense mutations in the CALM1 gene: D130G (<a href="#0003">114180.0003</a>) and F142L (<a href="#0004">114180.0004</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 a Moroccan family with mild prolongation of the QTc interval in the recovery phase after exercise as well as onset of ventricular fibrillation within the first 2 decades of life, <a href="#17" class="mim-tip-reference" title="Marsman, R. F., Barc, J., Beekman, L., Alders, M., Dooijes, D., van den Wijngaard, A., Ratbi, I., Sefiani, A., Bhuiyan, Z. A., Wilde, A. A. M., Bezzina, C. R. <strong>A mutation in CALM1 encoding calmodulin in familial idiopathic ventricular fibrillation in childhood and adolescence.</strong> J. Am. Coll. Cardiol. 63: 259-266, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24076290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24076290</a>] [<a href="https://doi.org/10.1016/j.jacc.2013.07.091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24076290">Marsman et al. (2014)</a> identified heterozygosity for a missense mutation in the CALM1 gene (F90L; <a href="#0005">114180.0005</a>), which segregated with disease in the family and was not found in 500 Moroccan controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24076290" 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="#16" 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> noted that mutations associated with CPVT do not impair calcium affinity to the same extent as those associated with LQTS. <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="#4" 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://www.ncbi.nlm.nih.gov/pmc/?term=26969752[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.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 3 unrelated patients with heterozygous mutations in the CALM1 gene, including 2 deceased children with the F142L mutation (<a href="#0004">114180.0004</a>) that had been reported previously in a 14-year-old Italian boy by <a href="#6" 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>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23388215+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="#7" 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://www.ncbi.nlm.nih.gov/pmc/?term=31170290[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/10.1093/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, CALM2 (<a href="/entry/114182">114182</a>), 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><p><strong><em>Association with Osteoarthritis</em></strong></p><p>
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In 2 independent Japanese populations totaling 428 osteoarthritis (OA; <a href="/entry/165720">165720</a>) patients and 1,008 controls, <a href="#20" class="mim-tip-reference" title="Mototani, H., Mabuchi, A., Saito, S., Fujioka, M., Iida, A., Takatori, Y., Kotani, A., Kubo, T., Nakamura, K., Sekine, A., Murakami, Y., Tsunoda, T., Notoya, K., Nakamura, Y., Ikegawa, S. <strong>A functional single nucleotide polymorphism in the core promoter region of CALM1 is associated with hip osteoarthritis in Japanese.</strong> Hum. Molec. Genet. 14: 1009-1017, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15746150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15746150</a>] [<a href="https://doi.org/10.1093/hmg/ddi093" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15746150">Mototani et al. (2005)</a> identified significant association between hip OA and a -16C-T promoter SNP (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs12885713;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs12885713</a>) in the CALM1 gene. Functional analysis indicated that the -16T allele decreased CALM1 transcription in vitro and in vivo. CALM1 was expressed in cultured chondrocytes and articular cartilage, and its expression was increased in OA. Inhibition of CALM1 in chondrogenic cells reduced expression of the major cartilage matrix genes COL2A1 (<a href="/entry/120140">120140</a>) and AGC1 (<a href="/entry/155760">155760</a>). <a href="#20" class="mim-tip-reference" title="Mototani, H., Mabuchi, A., Saito, S., Fujioka, M., Iida, A., Takatori, Y., Kotani, A., Kubo, T., Nakamura, K., Sekine, A., Murakami, Y., Tsunoda, T., Notoya, K., Nakamura, Y., Ikegawa, S. <strong>A functional single nucleotide polymorphism in the core promoter region of CALM1 is associated with hip osteoarthritis in Japanese.</strong> Hum. Molec. Genet. 14: 1009-1017, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15746150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15746150</a>] [<a href="https://doi.org/10.1093/hmg/ddi093" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15746150">Mototani et al. (2005)</a> suggested that the transcriptional level of CALM1 may be associated with susceptibility for hip OA through modulation of chondrogenic activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15746150" 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 classic textbook example of adaptive radiation under natural selection is the evolution of 14 closely related species of Darwin's finches, whose primary diversity lies in the size and shape of their beaks. The precise dimensions (length, depth, and width) of each species' beak are crucial to their lifestyle and survival, and fluctuations in the environment lead to selection that changes the relative success of birds with various beak shapes. These evolutionary processes are evident in real time on the Galapagos Islands (<a href="#10" class="mim-tip-reference" title="Grant, P. R., Grant, B. R. <strong>Evolution of character displacement in Darwin's finches.</strong> Science 313: 224-226, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16840700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16840700</a>] [<a href="https://doi.org/10.1126/science.1128374" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16840700">Grant and Grant, 2006</a>). <a href="#2" class="mim-tip-reference" title="Abzhanov, A., Protas, M., Grant, R. B., Grant, P. R., Tabin, C. J. <strong>Bmp4 and morphological variation of beaks in Darwin's finches.</strong> Science 305: 1462-1465, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15353802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15353802</a>] [<a href="https://doi.org/10.1126/science.1098095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15353802">Abzhanov et al. (2004)</a> showed that the BMP4 gene (<a href="/entry/112262">112262</a>), which plays a role in skeletal and cartilaginous development in mice, is more broadly expressed during the embryonic development of the deep and wide beaks of ground finches than during the development of finches with narrower beaks. Using a cDNA microarray analysis of the transcripts expressed in the beak primordia to find previously unknown genes and pathways whose expression correlates with specific beak morphologies, <a href="#1" class="mim-tip-reference" title="Abzhanov, A., Kuo, W. P., Hartmann, C., Grant, B. R., Grant, P. R., Tabin, C. J. <strong>The calmodulin pathway and evolution of elongated beak morphology in Darwin's finches.</strong> Nature 442: 563-567, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885984/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885984</a>] [<a href="https://doi.org/10.1038/nature04843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885984">Abzhanov et al. (2006)</a> found that calmodulin is expressed at much higher levels in the long and pointed beaks of cactus finch embryos than in the beaks of other finch embryos. They showed further that when upregulation of the calmodulin-dependent pathway is artificially replicated in the chick frontonasal prominence, it causes an elongation of the upper beak, recapitulating the beak morphology of the cactus finches. The results indicated that local upregulation of the calmodulin-dependent pathway is likely to have been a component in the evolution of Darwin's finch species with elongated beak morphology and provide a mechanistic explanation for the independence of beak evolution along different axes, e.g., broad versus elongated. More generally, their results implicated the calmodulin-dependent pathway in the developmental regulation of craniofacial skeletal structures. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16885984+15353802+16840700" 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="#24" class="mim-tip-reference" title="Scambler, P. J., McPherson, M. A., Bates, G., Bradbury, N. A., Dormer, R. L., Williamson, R. <strong>Biochemical and genetic exclusion of calmodulin as the site of the basic defect in cystic fibrosis.</strong> Hum. Genet. 76: 278-282, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2885258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2885258</a>] [<a href="https://doi.org/10.1007/BF00283623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2885258">Scambler et al. (1987)</a> identified a calmodulin-like locus, designated CALML1, on chromosome 7pter-p13 by study of somatic cell hybrids. Based on map and other indirect evidence, <a href="#26" class="mim-tip-reference" title="Scott, A. F. <strong>Personal Communication.</strong> Baltimore, Md. 2/8/2007."None>Scott (2007)</a> concluded that this locus is a pseudogene (CALM1P2). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2885258" 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">rs267607276 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607276;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=rs267607276" 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=rs267607276" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 10 affected members of a large 4-generation Swedish family with catecholaminergic polymorphic ventricular tachycardia (CPVT4; <a href="/entry/614916">614916</a>), <a href="#21" class="mim-tip-reference" title="Nyegaard, M., Overgaard, M. T., Sondergaard, M. T., Vranas, M., Behr, E. R., Hildebrandt, L. L., Lund, J., Hedley, P. L., Camm, A. J., Wettrell, G., Fosdal, I., Christiansen, M., Borglum, A. D. <strong>Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death.</strong> Am. J. Hum. Genet. 91: 703-712, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23040497/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23040497</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23040497[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.08.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23040497">Nyegaard et al. (2012)</a> identified heterozygosity for a 161A-T transversion in exon 3 of the CALM1 gene, resulting in an asn53-to-ile (N53I) substitution at a highly conserved residue within the first alpha-helix of Ca(2+)-binding site II. The mutation was not found in unaffected family members or in 1,200 controls. Functional analysis demonstrated that the mutant had significantly reduced Ca(2+) affinity compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23040497" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 4</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267607277 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607277;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=rs267607277" 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=rs267607277" 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=RCV000032977 OR RCV000157134 OR RCV000526484 OR RCV000714909 OR RCV002433484 OR RCV004758616" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032977, RCV000157134, RCV000526484, RCV000714909, RCV002433484, RCV004758616" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032977...</a>
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<p>In a 23-year-old Iraqi woman with catecholaminergic polymorphic ventricular tachycardia (CPVT4; <a href="/entry/614916">614916</a>), <a href="#21" class="mim-tip-reference" title="Nyegaard, M., Overgaard, M. T., Sondergaard, M. T., Vranas, M., Behr, E. R., Hildebrandt, L. L., Lund, J., Hedley, P. L., Camm, A. J., Wettrell, G., Fosdal, I., Christiansen, M., Borglum, A. D. <strong>Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death.</strong> Am. J. Hum. Genet. 91: 703-712, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23040497/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23040497</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23040497[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.08.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23040497">Nyegaard et al. (2012)</a> identified heterozygosity for a de novo 293A-G transition in exon 5 of the CALM1 gene, resulting in an asn97-to-ser (N97S) substitution at a highly conserved Ca(2+)-binding residue within the high-affinity binding-site III in the calmodulin C domain. The mutation was not found in her unaffected parents or in 500 Danish controls, and the patient was negative for mutation in 8 other arrhythmia-associated genes. At age 4 years, the patient underwent cardiac arrest due to ventricular fibrillation while running; she was stabilized by treatment with a beta-1 adrenergic receptor blocker. Electrocardiography (ECG) showed prominent U-waves in anterior leads but no evidence for long QT or Brugada syndromes. At 12 years of age, an off-medication exercise ECG demonstrated ventricular ectopy with couplets and triplets of varying morphology, which appeared to be bidirectional at times. At age 15, she suffered a second cardiac arrest and underwent implantation of an internal cardiac defibrillator (ICD). Functional analysis demonstrated that the mutant had significantly reduced Ca(2+) affinity compared to wildtype calmodulin. In addition, for the N97S mutant, calmodulin-RYR2 (<a href="/entry/180902">180902</a>) interaction was defective at low intracellular Ca(2+) concentrations and restored at moderate to high Ca(2+) concentrations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23040497" 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">rs730882252 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs730882252;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=rs730882252" 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=rs730882252" 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=RCV000162062 OR RCV001781506" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000162062, RCV001781506" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000162062...</a>
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<p>In an Italian girl and a Greek boy with markedly prolonged QTc intervals and early-onset life-threatening ventricular arrhythmias (LQT14; <a href="/entry/616247">616247</a>), <a href="#6" 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 an A-to-G transition in the CALM1 gene, resulting in an asp130-to-gly (D130G) substitution at a highly conserved residue in the EF-hand domain IV. The mutation, which occurred de novo in both patients, was not found in 1,800 white European controls or in the dbSNP (build 130), 1000 Genomes Project, Exome Variant Server, or Helmholtz databases. Functional analysis demonstrated a 53-fold reduction in calcium affinity with the D130G 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>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000162063" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000162063" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000162063</a>
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<p>In a 14-year-old Italian boy with a markedly prolonged QTc interval, recurrent episodes of nonsustained ventricular tachycardia, T-wave alternans, and cardiac arrest due to ventricular fibrillation (LQT14; <a href="/entry/616247">616247</a>), <a href="#6" 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 C-to-G transversion in the CALM1 gene, resulting in a phe142-to-leu (F142L) substitution at a highly conserved residue in the EF-hand domain IV. The mutation was not found in 1,800 white European controls or in the dbSNP (build 130), 1000 Genomes Project, Exome Variant Server, or Helmholtz databases. Functional analysis demonstrated a 5-fold reduction in calcium affinity with the F142L mutant compared to wildtype calmodulin. The patient, who was adopted at 8 years of age, had normal cardiac anatomy and contractile function on echocardiogram. <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 a girl who died at age 2 years and an unrelated boy who died at age 1.25 years with LQTS, <a href="#4" 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://www.ncbi.nlm.nih.gov/pmc/?term=26969752[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.115.001323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26969752">Boczek et al. (2016)</a> identified heterozygosity for the F142L mutation (c.426C-G, NM_006888) in the CALM1 gene. The mutation appeared to have arisen de novo in both patients; neither of the boy's parents nor the girl's mother carried the mutation, and DNA was unavailable from the girl's father. Prior to her death, echocardiogram in the girl showed severely diminished left ventricular systolic function, and autopsy revealed cardiomegaly with dilation and hypertrophy. <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>In a Moroccan family with mild prolongation of the QTc interval in the recovery phase after exercise as well as episodes of ventricular fibrillation within the first 2 decades of life (LQT14; <a href="/entry/616247">616247</a>), <a href="#17" class="mim-tip-reference" title="Marsman, R. F., Barc, J., Beekman, L., Alders, M., Dooijes, D., van den Wijngaard, A., Ratbi, I., Sefiani, A., Bhuiyan, Z. A., Wilde, A. A. M., Bezzina, C. R. <strong>A mutation in CALM1 encoding calmodulin in familial idiopathic ventricular fibrillation in childhood and adolescence.</strong> J. Am. Coll. Cardiol. 63: 259-266, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24076290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24076290</a>] [<a href="https://doi.org/10.1016/j.jacc.2013.07.091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24076290">Marsman et al. (2014)</a> identified heterozygosity for a c.268T-C transition in the CALM1 gene, resulting in a phe90-to-leu (F90L) substitution at a highly conserved residue between EF-hand domains II and III. The mutation was present in the mother and 4 affected sibs, but was not detected in the unaffected father, an unaffected sib, or 500 Moroccan controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24076290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<div class="">
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<a id="Abzhanov2004" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1126/science.1098095" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/geno.1993.1211" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1161/CIRCGENETICS.115.001323" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1074/jbc.272.50.31235" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1161/CIRCULATIONAHA.112.001216" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/eurheartj/ehz311" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/nature06529" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/415396a" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.1128374" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/s41586-023-06985-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.cell.2004.06.029" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/nature08766" target="_blank">Full Text</a>]
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<a id="Makita2014" class="mim-anchor"></a>
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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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[<a href="https://doi.org/10.1161/CIRCGENETICS.113.000459" target="_blank">Full Text</a>]
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Marsman, R. F., Barc, J., Beekman, L., Alders, M., Dooijes, D., van den Wijngaard, A., Ratbi, I., Sefiani, A., Bhuiyan, Z. A., Wilde, A. A. M., Bezzina, C. R.
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[<a href="https://doi.org/10.1016/j.jacc.2013.07.091" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.1093490" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddi093" target="_blank">Full Text</a>]
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<a id="Nyegaard2012" class="mim-anchor"></a>
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Nyegaard, M., Overgaard, M. T., Sondergaard, M. T., Vranas, M., Behr, E. R., Hildebrandt, L. L., Lund, J., Hedley, P. L., Camm, A. J., Wettrell, G., Fosdal, I., Christiansen, M., Borglum, A. D.
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[<a href="https://doi.org/10.1016/j.ajhg.2012.08.015" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0006-291x(90)91567-c" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1432-1033.1994.00071.x" target="_blank">Full Text</a>]
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<strong>Biochemical and genetic exclusion of calmodulin as the site of the basic defect in cystic fibrosis.</strong>
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[<a href="https://doi.org/10.1007/BF00283623" target="_blank">Full Text</a>]
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<strong>Structure of the gating domain of a Ca(2+)-activated K+ channel complexed with Ca(2+)/calmodulin.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11323678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11323678</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11323678" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/35074145" target="_blank">Full Text</a>]
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<a id="SenGupta1989" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1093/nar/17.7.2868" target="_blank">Full Text</a>]
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SenGupta, B., Friedberg, F., Detera-Wadleigh, S. D.
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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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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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[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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<span class="mim-text-font">
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Bao Lige - updated : 04/04/2024
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Marla J. F. O'Neill - updated : 02/26/2020<br>Marla J. F. O'Neill - updated : 02/20/2020<br>Marla J. F. O'Neill - updated : 2/26/2015<br>Marla J. F. O'Neill - updated : 11/6/2012<br>Ada Hamosh - updated : 4/22/2010<br>Ada Hamosh - updated : 3/7/2008<br>George E. Tiller - updated : 2/7/2008<br>Victor A. McKusick - updated : 9/26/2006<br>Stylianos E. Antonarakis - updated : 2/15/2005<br>Ada Hamosh - updated : 4/29/2004<br>Patricia A. Hartz - updated : 11/18/2002<br>Paul J. Converse - updated : 1/23/2002<br>Ada Hamosh - updated : 4/23/2001<br>Paul J. Converse - updated : 5/24/2000
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carol : 02/24/2022<br>alopez : 02/26/2020<br>alopez : 02/26/2020<br>carol : 02/24/2020<br>alopez : 02/21/2020<br>carol : 02/21/2020<br>alopez : 02/20/2020<br>carol : 12/10/2016<br>carol : 12/09/2016<br>carol : 12/08/2016<br>alopez : 10/06/2016<br>alopez : 03/02/2015<br>mcolton : 2/26/2015<br>carol : 11/6/2012<br>terry : 11/6/2012<br>alopez : 6/17/2010<br>alopez : 4/26/2010<br>terry : 4/22/2010<br>alopez : 3/20/2008<br>terry : 3/7/2008<br>wwang : 2/14/2008<br>terry : 2/7/2008<br>terry : 9/17/2007<br>carol : 2/8/2007<br>carol : 10/13/2006<br>terry : 9/26/2006<br>mgross : 2/15/2005<br>mgross : 2/15/2005<br>alopez : 5/4/2004<br>terry : 4/29/2004<br>mgross : 11/18/2002<br>alopez : 1/23/2002<br>alopez : 4/25/2001<br>terry : 4/23/2001<br>mgross : 5/24/2000<br>mgross : 5/24/2000<br>terry : 11/13/1998<br>mark : 11/11/1997<br>mark : 12/29/1996<br>carol : 1/19/1995<br>carol : 12/23/1993<br>carol : 5/26/1993<br>carol : 8/14/1992<br>supermim : 3/16/1992<br>carol : 3/9/1992
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<span class="mim-font">
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<strong>*</strong> 114180
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</h3>
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<h3>
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<span class="mim-font">
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CALMODULIN 1; CALM1
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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PHOSPHORYLASE KINASE, DELTA SUBUNIT; PHKD
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: CALM1</em></strong>
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</span>
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</p>
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<strong>
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<em>
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Cytogenetic location: 14q32.11
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Genomic coordinates <span class="small">(GRCh38)</span> : 14:90,396,502-90,408,268 </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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</p>
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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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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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14q32.11
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<span class="mim-font">
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Long QT syndrome 14
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<span class="mim-font">
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616247
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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<span class="mim-font">
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Ventricular tachycardia, catecholaminergic polymorphic, 4
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<span class="mim-font">
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614916
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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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, CALM2 (114182), 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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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</h4>
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<p>Until the studies of SenGupta et al. (1987), only 1 human calmodulin cDNA had been reported. These authors found evidence of a second actively transcribed calmodulin gene in man. Calmodulin is the delta subunit of phosphorylase kinase, which has 3 other types of subunits. Although only 1 form of calmodulin has been found in humans, 3 distinct human cDNAs have been isolated that encode the identical polypeptide (Koller et al., 1990; Pegues and Friedberg, 1990). The existence of 3 expressible genes for calmodulin may indicate that one is a housekeeping gene and that the additional copies are differentially regulated to modulate calmodulin function. </p><p>Rhyner et al. (1994) detected expression of CALM1 in all human tissues tested, although at varying levels. They identified 2 different CALM1-related pseudogenes. </p><p>Toutenhoofd et al. (1998) found that all 3 CALM genes were expressed in human teratocarcinoma cells. CALM1 was expressed as a major 1.7-kb transcript and a minor 4.1-kb transcript. CALM1 was at least 5-fold less actively transcribed than CALM3 (114183). </p>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>To determine how calcium/calmodulin activates calcium/calmodulin-dependent protein kinase I (CAMK1; 604998), Chin et al. (1997) characterized CAMK1 activation by calmodulin mutants with substitutions at hydrophobic residues. They found that CAMK1 activity is dependent on met124 within the C-terminal domain of calmodulin as well as on N-terminal hydrophobic residues of calmodulin. </p><p>Kretsinger et al. (1986) described the crystal structure of calmodulin to 3.6-angstrom resolution. </p><p>Schumacher et al. (2001) determined the crystal structure of calmodulin bound to KCNN2 (605879). The calmodulin-binding domain forms an elongated dimer with a calmodulin molecule bound at each end; each calmodulin wraps around 3 alpha-helices, 2 from 1 calmodulin-binding domain subunit and 1 from the other. </p><p>Edema factor, the exotoxin of the anthrax bacillus, is transported into host cells by an anthrax-derived transporter, protective antigen. Together with lethal factor (see 603060), edema factor contributes significantly to both cutaneous and systemic anthrax and is an adenylyl cyclase activated by CALM1. Drum et al. (2002) described the crystal structures of edema factor alone and edema factor with CALM1 and 3-prime-deoxy-ATP. On calmodulin binding, an edema factor helical domain of 15 kD undergoes a 15-angstrom translation and a 30-degree rotation away from the edema factor catalytic core, which stabilizes a disordered loop and leads to enzyme activation. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Rhyner et al. (1994) found that the CALM1 gene contains 6 exons spread over about 10 kb of genomic DNA. The exon-intron structure was identical to that of CALM3. A cluster of transcription-start sites was identified 200 bp upstream of the ATG translation-start codon, and several putative regulatory elements were found in the 5-prime flanking region, as well as in intron 1. A short CAG trinucleotide repeat region was identified in the 5-prime untranslated region of the gene. </p><p>Toutenhoofd et al. (1998) determined that of the 3 CALM genes, only CALM1 contains a canonical TATA box. Like CALM3, the 5-prime region of CALM1 is highly GC rich. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>McPherson et al. (1991) used a panel of human/rodent somatic cell hybrids to demonstrate that the cDNA probe for CALM1 was localized to chromosome 14 with cross-hybridization evident on chromosome 7 and very weak on the X chromosome. The assignments to chromosomes 14 and 7 confirmed an earlier report by Scambler et al. (1987). McPherson et al. (1991) tentatively assigned the CALM2 (114182) gene to chromosome 10, but the gene was subsequently shown to be on chromosome 2. They assigned the cDNA probe for CALM3 unequivocally to chromosome 19. There was no apparent cross-hybridization to other chromosomes. A calmodulin pseudogene is located on chromosome 17 (SenGupta et al., 1989) and there are probably more on several other chromosomes. Berchtold et al. (1993) assigned the CALM1 gene to chromosome 14 by PCR-based amplification of CALM1-specific sequences using DNA from human/hamster cell hybrids as template. Regional sublocalization was performed by in situ hybridization using CALM1-specific DNA probes of intronic or flanking parts of the gene; the regional localization was found to be 14q24-q31. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>To understand the relationship between the number of calmodulin molecules regulating each L-type calcium channel (see 114205) and the number of calmodulin molecules privy to the local calcium signal from each channel, Mori et al. (2004) fused L-type calcium channels to single calmodulin molecules. These chimeric molecules revealed that a single calmodulin molecule directs L-type channel regulation. Similar fusion molecules were used to estimate the local calmodulin concentration near calcium channels. This estimate indicates marked enrichment of local calmodulin, as if a school of nearby calmodulins were poised to enhance the transduction of local calcium entry into diverse signaling pathways. </p><p>Junge et al. (2004) identified a conserved calmodulin-binding site in Munc13s (see 605836), which are essential regulators of synaptic vesicle priming and synaptic efficacy. They showed that Ca(2+) sensor/effector complexes consisting of calmodulin and Munc13s regulate synaptic vesicle priming and synaptic efficacy in response to a residual Ca(2+) concentration signal and thus shape short-term plasticity characteristics during periods of sustained synaptic activity. </p><p>Dick et al. (2008) showed that the spatial calcium ion selectivity of N-lobe calmodulin regulation is not invariably global but can be switched by a novel calcium ion/calmodulin binding site within the amino terminus of channels (NSCaTE, for N-terminal spatial calcium ion transforming element). Native Ca(v)2.2 channels lack this element and show N-lobe regulation with a global selectivity. On the introduction of NSCaTE into these channels, spatial calcium ion selectivity transforms from a global to local profile. Given this effect, Dick et al. (2008) examined Ca(v)1.2/Ca(v)1.3 channels, which naturally contain NSCaTE, and found that their N-lobe selectivity is indeed local. Disruption of this element produces a global selectivity, confirming the native function of NSCaTE. Thus, Dick et al. (2008) concluded that differences in spatial selectivity between advanced Ca(v)1 and Ca(v)2 channel isoforms are explained by the presence or absence of NSCaTE. Beyond functional effects, the position of NSCaTE on the channel's amino terminus indicates that calmodulin can bridge the amino terminus and carboxy terminus of channels. Finally, the modularity of NSCaTE offers practical means for understanding the basis of global calcium ion selectivity. </p><p>Liu et al. (2010) combined electrophysiology to characterize channel regulation with optical fluorescence resonance energy transfer (FRET) sensor determination of free-apoCaM concentration in live cells. This approach translates quantitative calmodulin biochemistry from the traditional test-tube context into the realm of functioning holochannels within intact cells. From this perspective, Liu et al. (2010) found that long splice forms of Ca(V)1.3 (CACNA1D; 114206) and Ca(V)1.4 (CACNA1F; 300110) channels include a distal carboxy tail that resembles an enzyme competitive inhibitor that retunes channel affinity for apocalmodulin such that natural calmodulin variations affect the strength of Ca(2+) feedback modulation. Given the ubiquity of these channels, the connection between ambient calmodulin levels and Ca(2+) entry through channels is broadly significant for Ca(2+) homeostasis. </p><p>By knockout analysis in HEK293T cells, Haakonsen et al. (2024) demonstrated that the E3 ligase UBR4 (609890) was important when mitochondrial function was compromised. UBR4 bound KCMF1 (614719) and calmodulin to form an E3 ligase complex that sustained survival of cells undergoing mitochondrial import stress. The authors named the UBR4-KCMF1-calmodulin complex 'silencing factor of the integrated stress response,' or SIFI. SIFI targeted HRI (613635) and the cytosolic cleavage fragment of DELE1 (615741) (cDELE1), proteins that actively mediate the cellular response to mitochondrial import stress, to promote their ubiquitylation and degradation to silence the integrated stress response in cells. The N terminus of HRI contains 2 alpha helices that served as degrons, with each capable of mediating recognition by SIFI. Multiple motifs in cDELE1, including an N-terminal motif that was exposed after cleavage and a helix with similarity to HRI degrons, were recognized by SIFI. The helical HRI and cDELE1 degrons closely resembled mitochondrial presequences. Consequently, SIFI not only recognized and targeted HRI and cDELE1, but it also appeared to target other proteins containing a presequence, including unimported mitochondrial proteins that accumulated in the cytoplasm during import stress, for their ubiquitylation and degradation. Ubiquitylation of presequences depended on the calmodulin and KCMF1 subunits of SIFI. These mitochondrial presequences and cDELE1 and HRI degrons, which were similar to stress response degrons, were related bifunctional motifs that could be recognized by both the mitochondrial import machinery and SIFI. Consequently, these converging degrons were able to couple stress resolution to stress response silencing in cells. Further analysis revealed that HRI and DELE1 mediated stress response signaling without affecting mitochondrial protein import, and pharmacologic silencing of the stress response restored survival of UBR4- or KCMF1-knockout cells that failed to resolve mitochondrial stress. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
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<p><strong><em>Catecholaminergic Polymorphic Ventricular Tachycardia 4</em></strong></p><p>
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In a large 4-generation Swedish family with autosomal dominant catecholaminergic polymorphic ventricular tachycardia (CPVT4; 614916), Nyegaard et al. (2012) identified heterozygosity for a missense mutation in the CALM1 gene (N53I; 114180.0001) that segregated fully with disease in the family and was not found in 1,200 controls. A de novo missense mutation in CALM1 (N97S; 114180.0002) was subsequently identified in a 23-year-old Iraqi woman with a history of cardiac arrest at 4 years of age due to ventricular fibrillation while running. Both substitutions demonstrated compromised calcium binding. </p><p><strong><em>Long QT Syndrome 14</em></strong></p><p>
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In 3 children with markedly prolonged QTc intervals and life-threatening ventricular arrhythmias (LQT14; 616247), Crotti et al. (2013) identified heterozygosity for de novo missense mutations in the CALM1 gene: D130G (114180.0003) and F142L (114180.0004). </p><p>In a Moroccan family with mild prolongation of the QTc interval in the recovery phase after exercise as well as onset of ventricular fibrillation within the first 2 decades of life, Marsman et al. (2014) identified heterozygosity for a missense mutation in the CALM1 gene (F90L; 114180.0005), which segregated with disease in the family and was not found in 500 Moroccan controls. </p><p>Makita et al. (2014) noted that mutations associated with CPVT do not impair calcium affinity to the same extent as those associated with LQTS. </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 3 unrelated patients with heterozygous mutations in the CALM1 gene, including 2 deceased children with the F142L mutation (114180.0004) that had been reported previously in a 14-year-old Italian boy by Crotti et al. (2013). </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, CALM2 (114182), 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><p><strong><em>Association with Osteoarthritis</em></strong></p><p>
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In 2 independent Japanese populations totaling 428 osteoarthritis (OA; 165720) patients and 1,008 controls, Mototani et al. (2005) identified significant association between hip OA and a -16C-T promoter SNP (rs12885713) in the CALM1 gene. Functional analysis indicated that the -16T allele decreased CALM1 transcription in vitro and in vivo. CALM1 was expressed in cultured chondrocytes and articular cartilage, and its expression was increased in OA. Inhibition of CALM1 in chondrogenic cells reduced expression of the major cartilage matrix genes COL2A1 (120140) and AGC1 (155760). Mototani et al. (2005) suggested that the transcriptional level of CALM1 may be associated with susceptibility for hip OA through modulation of chondrogenic activity. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</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>A classic textbook example of adaptive radiation under natural selection is the evolution of 14 closely related species of Darwin's finches, whose primary diversity lies in the size and shape of their beaks. The precise dimensions (length, depth, and width) of each species' beak are crucial to their lifestyle and survival, and fluctuations in the environment lead to selection that changes the relative success of birds with various beak shapes. These evolutionary processes are evident in real time on the Galapagos Islands (Grant and Grant, 2006). Abzhanov et al. (2004) showed that the BMP4 gene (112262), which plays a role in skeletal and cartilaginous development in mice, is more broadly expressed during the embryonic development of the deep and wide beaks of ground finches than during the development of finches with narrower beaks. Using a cDNA microarray analysis of the transcripts expressed in the beak primordia to find previously unknown genes and pathways whose expression correlates with specific beak morphologies, Abzhanov et al. (2006) found that calmodulin is expressed at much higher levels in the long and pointed beaks of cactus finch embryos than in the beaks of other finch embryos. They showed further that when upregulation of the calmodulin-dependent pathway is artificially replicated in the chick frontonasal prominence, it causes an elongation of the upper beak, recapitulating the beak morphology of the cactus finches. The results indicated that local upregulation of the calmodulin-dependent pathway is likely to have been a component in the evolution of Darwin's finch species with elongated beak morphology and provide a mechanistic explanation for the independence of beak evolution along different axes, e.g., broad versus elongated. More generally, their results implicated the calmodulin-dependent pathway in the developmental regulation of craniofacial skeletal structures. </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>History</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>Scambler et al. (1987) identified a calmodulin-like locus, designated CALML1, on chromosome 7pter-p13 by study of somatic cell hybrids. Based on map and other indirect evidence, Scott (2007) concluded that this locus is a pseudogene (CALM1P2). </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>5 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 4</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CALM1, ASN53ILE
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<br />
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SNP: rs267607276,
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ClinVar: RCV000032976, RCV000157133
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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 10 affected members of a large 4-generation Swedish family with catecholaminergic polymorphic ventricular tachycardia (CPVT4; 614916), Nyegaard et al. (2012) identified heterozygosity for a 161A-T transversion in exon 3 of the CALM1 gene, resulting in an asn53-to-ile (N53I) substitution at a highly conserved residue within the first alpha-helix of Ca(2+)-binding site II. The mutation was not found in unaffected family members or in 1,200 controls. Functional analysis demonstrated that the mutant had significantly reduced Ca(2+) affinity compared to wildtype. </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 VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 4</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CALM1, ASN97SER
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<br />
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SNP: rs267607277,
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ClinVar: RCV000032977, RCV000157134, RCV000526484, RCV000714909, RCV002433484, RCV004758616
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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 23-year-old Iraqi woman with catecholaminergic polymorphic ventricular tachycardia (CPVT4; 614916), Nyegaard et al. (2012) identified heterozygosity for a de novo 293A-G transition in exon 5 of the CALM1 gene, resulting in an asn97-to-ser (N97S) substitution at a highly conserved Ca(2+)-binding residue within the high-affinity binding-site III in the calmodulin C domain. The mutation was not found in her unaffected parents or in 500 Danish controls, and the patient was negative for mutation in 8 other arrhythmia-associated genes. At age 4 years, the patient underwent cardiac arrest due to ventricular fibrillation while running; she was stabilized by treatment with a beta-1 adrenergic receptor blocker. Electrocardiography (ECG) showed prominent U-waves in anterior leads but no evidence for long QT or Brugada syndromes. At 12 years of age, an off-medication exercise ECG demonstrated ventricular ectopy with couplets and triplets of varying morphology, which appeared to be bidirectional at times. At age 15, she suffered a second cardiac arrest and underwent implantation of an internal cardiac defibrillator (ICD). Functional analysis demonstrated that the mutant had significantly reduced Ca(2+) affinity compared to wildtype calmodulin. In addition, for the N97S mutant, calmodulin-RYR2 (180902) interaction was defective at low intracellular Ca(2+) concentrations and restored at moderate to high Ca(2+) concentrations. </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 14</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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CALM1, ASP130GLY
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<br />
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SNP: rs730882252,
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ClinVar: RCV000162062, RCV001781506
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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 an Italian girl and a Greek boy with markedly prolonged QTc intervals and early-onset life-threatening ventricular arrhythmias (LQT14; 616247), Crotti et al. (2013) identified heterozygosity for an A-to-G transition in the CALM1 gene, resulting in an asp130-to-gly (D130G) substitution at a highly conserved residue in the EF-hand domain IV. The mutation, which occurred de novo in both patients, was not found in 1,800 white European controls or in the dbSNP (build 130), 1000 Genomes Project, Exome Variant Server, or Helmholtz databases. Functional analysis demonstrated a 53-fold reduction in calcium affinity with the D130G 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>.0004 LONG QT SYNDROME 14</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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CALM1, PHE142LEU
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<br />
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SNP: rs199744595,
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gnomAD: rs199744595,
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ClinVar: RCV000162063
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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 14-year-old Italian boy with a markedly prolonged QTc interval, recurrent episodes of nonsustained ventricular tachycardia, T-wave alternans, and cardiac arrest due to ventricular fibrillation (LQT14; 616247), Crotti et al. (2013) identified heterozygosity for a C-to-G transversion in the CALM1 gene, resulting in a phe142-to-leu (F142L) substitution at a highly conserved residue in the EF-hand domain IV. The mutation was not found in 1,800 white European controls or in the dbSNP (build 130), 1000 Genomes Project, Exome Variant Server, or Helmholtz databases. Functional analysis demonstrated a 5-fold reduction in calcium affinity with the F142L mutant compared to wildtype calmodulin. The patient, who was adopted at 8 years of age, had normal cardiac anatomy and contractile function on echocardiogram. </p><p>In a girl who died at age 2 years and an unrelated boy who died at age 1.25 years with LQTS, Boczek et al. (2016) identified heterozygosity for the F142L mutation (c.426C-G, NM_006888) in the CALM1 gene. The mutation appeared to have arisen de novo in both patients; neither of the boy's parents nor the girl's mother carried the mutation, and DNA was unavailable from the girl's father. Prior to her death, echocardiogram in the girl showed severely diminished left ventricular systolic function, and autopsy revealed cardiomegaly with dilation and hypertrophy. </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>.0005 LONG QT SYNDROME 14</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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CALM1, PHE90LEU
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<br />
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SNP: rs730882253,
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ClinVar: RCV000162064
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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 Moroccan family with mild prolongation of the QTc interval in the recovery phase after exercise as well as episodes of ventricular fibrillation within the first 2 decades of life (LQT14; 616247), Marsman et al. (2014) identified heterozygosity for a c.268T-C transition in the CALM1 gene, resulting in a phe90-to-leu (F90L) substitution at a highly conserved residue between EF-hand domains II and III. The mutation was present in the mother and 4 affected sibs, but was not detected in the unaffected father, an unaffected sib, or 500 Moroccan controls. </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>REFERENCES</strong>
|
|
</span>
|
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</h4>
|
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<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">
|
|
Abzhanov, A., Kuo, W. P., Hartmann, C., Grant, B. R., Grant, P. R., Tabin, C. J.
|
|
<strong>The calmodulin pathway and evolution of elongated beak morphology in Darwin's finches.</strong>
|
|
Nature 442: 563-567, 2006.
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|
[PubMed: 16885984]
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[Full Text: https://doi.org/10.1038/nature04843]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Abzhanov, A., Protas, M., Grant, R. B., Grant, P. R., Tabin, C. J.
|
|
<strong>Bmp4 and morphological variation of beaks in Darwin's finches.</strong>
|
|
Science 305: 1462-1465, 2004.
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|
|
[PubMed: 15353802]
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[Full Text: https://doi.org/10.1126/science.1098095]
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</p>
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</li>
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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">
|
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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.
|
|
<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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Chin, D., Winkler, K. E., Means, A. R.
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<strong>Characterization of substrate phosphorylation and use of calmodulin mutants to address implications from the enzyme crystal structure of calmodulin-dependent protein kinase I.</strong>
|
|
J. Biol. Chem. 272: 31235-31240, 1997.
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[PubMed: 9395448]
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[Full Text: https://doi.org/10.1074/jbc.272.50.31235]
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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">
|
|
Dick, I. E., Tadross, M. R., Liang, H., Tay, L. H., Yang, W., Yue, D. T.
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<strong>A modular switch for spatial Ca(2+) selectivity in the calmodulin regulation of Ca(v) channels.</strong>
|
|
Nature 451: 830-834, 2008.
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[PubMed: 18235447]
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[Full Text: https://doi.org/10.1038/nature06529]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Drum, C. L., Yan, S.-Z., Bard, J., Shen, Y.-Q., Lu, D., Soelaiman, S., Grabarek, Z., Bohm, A., Tang, W.-J.
|
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<strong>Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin.</strong>
|
|
Nature 415: 396-402, 2002.
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[PubMed: 11807546]
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[Full Text: https://doi.org/10.1038/415396a]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Grant, P. R., Grant, B. R.
|
|
<strong>Evolution of character displacement in Darwin's finches.</strong>
|
|
Science 313: 224-226, 2006.
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|
|
[PubMed: 16840700]
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|
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[Full Text: https://doi.org/10.1126/science.1128374]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Haakonsen, D. L., Heider, M., Ingersoll, A. J., Vodehnal, K., Witus, S. R., Uenaka, T., Wernig, M., Rape, M.
|
|
<strong>Stress response silencing by an E3 ligase mutated in neurodegeneration.</strong>
|
|
Nature 626: 874-880, 2024.
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|
[PubMed: 38297121]
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[Full Text: https://doi.org/10.1038/s41586-023-06985-7]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Junge, H. J., Rhee, J.-S., Jahn, O., Varoqueaux, F., Spiess, J., Waxham, M. N., Rosenmund, C., Brose, N.
|
|
<strong>Calmodulin and Munc13 form a Ca(2+) sensor/effector complex that controls short-term synaptic plasticity.</strong>
|
|
Cell 118: 389-401, 2004.
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[PubMed: 15294163]
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[Full Text: https://doi.org/10.1016/j.cell.2004.06.029]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Koller, M., Schnyder, B., Strehler, E. E.
|
|
<strong>Structural organization of the human CaMIII calmodulin gene.</strong>
|
|
Biochim. Biophys. Acta 1087: 180-189, 1990.
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|
|
[PubMed: 2223880]
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[Full Text: https://doi.org/10.1016/0167-4781(90)90203-e]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Kretsinger, R. H., Rudnick, S. E., Weissman, L. J.
|
|
<strong>Crystal structure of calmodulin.</strong>
|
|
J. Inorg. Biochem. 28: 289-302, 1986.
|
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|
|
[PubMed: 3806094]
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[Full Text: https://doi.org/10.1016/0162-0134(86)80093-9]
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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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