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Entry
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- *118507 - CHOLINERGIC RECEPTOR, NEURONAL NICOTINIC, BETA POLYPEPTIDE 2; CHRNB2
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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">*118507</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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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#geneFunction">Gene Function</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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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/118507">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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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=ENSG00000160716;t=ENST00000368476" 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=1141" 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=118507" 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=ENSG00000160716;t=ENST00000368476" 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_000748,XM_017000180,XR_001736952" 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_000748" 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=118507" 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=00335&isoform_id=00335_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/CHRNB2" 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/32017,113105,1458122,1702918,3766451,4502833,5579088,29891594,49901717,49902525,119573577,189069223,1034555103,2462502654" 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/P17787" 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=1141" 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=ENSG00000160716;t=ENST00000368476" 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=CHRNB2" 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=CHRNB2" 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+1141" 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/CHRNB2" 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:1141" 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/1141" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr1&hgg_gene=ENST00000368476.4&hgg_start=154567778&hgg_end=154580013&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:1962" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/chrnb2" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=118507[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=118507[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/CHRNB2/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000160716" 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=CHRNB2" 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=CHRNB2" 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=CHRNB2" 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=CHRNB2&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/PA115" 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:1962" 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/FBgn0000036.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:87891" 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/CHRNB2#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:87891" 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/1141/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=1141" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000047;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000047 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00006774;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00006774 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00006797;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00006797 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-070821-3" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1141" 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=CHRNB2&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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118507
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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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CHOLINERGIC RECEPTOR, NEURONAL NICOTINIC, BETA POLYPEPTIDE 2; CHRNB2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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ACETYLCHOLINE RECEPTOR, NEURONAL NICOTINIC, BETA-2 SUBUNIT
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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=CHRNB2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CHRNB2</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/1/1193?start=-3&limit=10&highlight=1193">1q21.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:154567778-154580013&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">1:154,567,778-154,580,013</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/1/1193?start=-3&limit=10&highlight=1193">
|
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1q21.3
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Epilepsy, nocturnal frontal lobe, 3
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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<a href="/entry/605375"> 605375 </a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/118507" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<p>The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are thought to be heteropentamers composed of homologous subunits. See <a href="/entry/118508">118508</a> for additional background information on nAChRs.</p>
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<p><a href="#1" class="mim-tip-reference" title="Anand, R., Lindstrom, J. <strong>Nucleotide sequence of the human nicotinic acetylcholine receptor beta-2 subunit gene.</strong> Nucleic Acids Res. 18: 4272, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2377478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2377478</a>] [<a href="https://doi.org/10.1093/nar/18.14.4272" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2377478">Anand and Lindstrom (1990)</a> isolated the beta-2 nAChR subunit by screening human fetal brain cDNA libraries with chicken beta-2 as a probe. The predicted 501-amino acid protein has a putative 25-amino acid signal peptide, and is 95% identical to rat beta-2 protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2377478" 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="Groot Kormelink, P. J., Luyten, W. H. M. L. <strong>Cloning and sequence of full-length cDNAs encoding the human neuronal nicotinic acetylcholine receptor (nAChR) subunits beta-3 and beta-4 and expression of seven nAChR subunits in the human neuroblastoma cell line SH-SY5Y and/or IMR-32.</strong> FEBS Lett. 400: 309-314, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9009220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9009220</a>] [<a href="https://doi.org/10.1016/s0014-5793(96)01383-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9009220">Groot Kormelink and Luyten (1997)</a> also isolated human beta-2 cDNAs from neuroblastoma cell lines and from frontal cortex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9009220" 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="#16" class="mim-tip-reference" title="Rempel, N., Heyers, S., Engels, H., Sleegers, E., Steinlein, O. K. <strong>The structures of the human neuronal nicotinic acetylcholine receptor beta-2- and alpha-3-subunit genes (CHRNB2 and CHRNA3).</strong> Hum. Genet. 103: 645-653, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921897</a>] [<a href="https://doi.org/10.1007/s004390050885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921897">Rempel et al. (1998)</a> determined that the CHRNB2 gene comprises 6 exons and spans approximately 9 kb of genomic DNA from the ATG start codon to the TGA stop codon. Exon 1 contains the 5-prime untranslated region, the ATG start codon, and parts of the sequence coding for the putative signal peptide. The hydrophobic transmembrane domains I through III are located in the large exon 5. Exon 6 contains the transmembrane domain IV as well as the translation stop codon and the 3-prime untranslated region. The CHRNB2 introns vary in size from 150 bp (intron 2) to 4.5 kb (intron 5). The splicing at the junctions of CHRNB2 introns 2, 3, and 5 occurred between codons (splicing type 0). Introns 1 and 4 were spliced after the first base (splicing type 1) and the second base of the codon (splicing type 2), respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921897" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Elliott, K. J., Ellis, S. B., Berckhan, K. J., Urrutia, A., Chavez-Noriega, L. E., Johnson, E. C., Velicelebi, G., Harpold, M. M. <strong>Comparative structure of human neuronal alpha(2)-alpha(7) and beta(2)-beta(4) nicotinic acetylcholine receptor subunits and functional expression of the alpha(2), alpha(3), alpha(4), alpha(7), beta(2), and beta(4) subunits.</strong> J. Molec. Neurosci. 7: 217-228, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8906617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8906617</a>] [<a href="https://doi.org/10.1007/BF02736842" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8906617">Elliott et al. (1996)</a> demonstrated that human beta-2 encodes a functional receptor when expressed in combination with human alpha-2 (CHRNA2; <a href="/entry/118502">118502</a>), alpha-3 (CHRNA3; <a href="/entry/118503">118503</a>), or alpha-4 (CHRNA4; <a href="/entry/118504">118504</a>) in Xenopus oocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8906617" 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 immunoprecipitation analysis of mouse striatal extracts, <a href="#4" class="mim-tip-reference" title="Champtiaux, N., Gotti, C., Cordero-Erausquin, M., David, D. J., Przybylski, C., Lena, C., Clementi, F., Moretti, M., Rossi, F. M., Le Novere, N., McIntosh, J. M., Gardier, A. M., Changeux, J.-P. <strong>Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice.</strong> J. Neurosci. 23: 7820-7829, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12944511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12944511</a>] [<a href="https://doi.org/10.1523/JNEUROSCI.23-21-07820.2003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12944511">Champtiaux et al. (2003)</a> identified 3 main types of heteromeric nAChRs: alpha-4/beta-2, alpha-6 (CHRNA6; <a href="/entry/606888">606888</a>)/beta-2, and alpha-4/alpha-6/beta-2. Alpha-6/beta-2 nAChRs were mainly located on dopamine (DA) nerve terminals and were the direct target of alpha-conotoxin MII inhibition. A combination of alpha-6/beta-2 and alpha-4/beta-2 nAChRs mediated endogenous cholinergic modulation of DA release induced by systemic nicotine administration at nerve terminals. Alpha-4/beta-2 nAChRs appeared to represent the majority of nAChRs on DA neuron soma and contributed to nicotine reinforcement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12944511" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Maskos, U., Molles, B. E., Pons, S., Besson, M., Guiard, B. P., Guilloux, J.-P., Evrard, A., Cazala, P., Cormier, A., Mameli-Engvall, M., Dufour, N., Cloez-Tayarani, I., Bemelmans, A.-P., Mallet, J., Gardier, A. M., David, V., Faure, P., Granon, S., Changeux, J.-P. <strong>Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors.</strong> Nature 436: 103-107, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16001069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16001069</a>] [<a href="https://doi.org/10.1038/nature03694" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16001069">Maskos et al. (2005)</a> reexpressed the beta-2 subunit of the nicotinic acetylcholine receptor by stereotaxically injecting a lentiviral vector into the ventral tegmental area of mice carrying beta-2 subunit deletions. <a href="#13" class="mim-tip-reference" title="Maskos, U., Molles, B. E., Pons, S., Besson, M., Guiard, B. P., Guilloux, J.-P., Evrard, A., Cazala, P., Cormier, A., Mameli-Engvall, M., Dufour, N., Cloez-Tayarani, I., Bemelmans, A.-P., Mallet, J., Gardier, A. M., David, V., Faure, P., Granon, S., Changeux, J.-P. <strong>Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors.</strong> Nature 436: 103-107, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16001069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16001069</a>] [<a href="https://doi.org/10.1038/nature03694" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16001069">Maskos et al. (2005)</a> demonstrated the efficient reexpression of electrophysiologically responsive, ligand-binding nicotinic acetylcholine receptors in DA-containing neurons of the ventral tegmental area, together with the recovery of nicotine-elicited DA release and nicotine self-administration. <a href="#13" class="mim-tip-reference" title="Maskos, U., Molles, B. E., Pons, S., Besson, M., Guiard, B. P., Guilloux, J.-P., Evrard, A., Cazala, P., Cormier, A., Mameli-Engvall, M., Dufour, N., Cloez-Tayarani, I., Bemelmans, A.-P., Mallet, J., Gardier, A. M., David, V., Faure, P., Granon, S., Changeux, J.-P. <strong>Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors.</strong> Nature 436: 103-107, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16001069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16001069</a>] [<a href="https://doi.org/10.1038/nature03694" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16001069">Maskos et al. (2005)</a> also quantified exploratory behaviors of the mice, and showed that beta-2 subunit reexpression restored slow exploratory behavior (a measure of cognitive function) to wildtype levels, but did not affect fast navigation behavior. <a href="#13" class="mim-tip-reference" title="Maskos, U., Molles, B. E., Pons, S., Besson, M., Guiard, B. P., Guilloux, J.-P., Evrard, A., Cazala, P., Cormier, A., Mameli-Engvall, M., Dufour, N., Cloez-Tayarani, I., Bemelmans, A.-P., Mallet, J., Gardier, A. M., David, V., Faure, P., Granon, S., Changeux, J.-P. <strong>Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors.</strong> Nature 436: 103-107, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16001069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16001069</a>] [<a href="https://doi.org/10.1038/nature03694" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16001069">Maskos et al. (2005)</a> concluded that their data demonstrated the sufficient role of the ventral tegmental area in both nicotine reinforcement and endogenous cholinergic regulation of cognitive functions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16001069" 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="#18" class="mim-tip-reference" title="Xiu, X., Puskar, N. L., Shanata, J. A. P., Lester, H. A., Dougherty, D. A. <strong>Nicotine binding to brain receptors requires a strong cation-pi interaction.</strong> Nature 458: 534-537, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19252481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19252481</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19252481[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/nature07768" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19252481">Xiu et al. (2009)</a> showed that at the brain acetylcholine receptors alpha-4-beta-2 thought to underlie nicotine addiction, the high affinity for nicotine is the result of a strong cation-pi interaction to a specific aromatic amino acid of the receptor, TrpB. In contrast, the low affinity for nicotine at the muscle-type acetylcholine receptor is largely due to the absence of this key interaction, even though the immediate binding site residues, including the key amino acid TrpB, are identical in the brain and muscle receptors. At the same time a hydrogen bond from nicotine to the backbone carbonyl of TrpB is enhanced in the neuronal receptor relative to the muscle type. A point mutation near TrpB that differentiates alpha-4-beta-2 and muscle-type receptors seems to influence the shape of the binding site, allowing nicotine to interact more strongly with TrpB in the neuronal receptor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19252481" 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>Cryoelectron Microscopy</em></strong></p><p>
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<a href="#17" class="mim-tip-reference" title="Walsh, R. M., Jr., Roh, S.-H., Gharpure, A., Morales-Perez, C. L., Teng, J., Hibbs, R. E. <strong>Structural principles of distinct assemblies of the human alpha-4-beta-2 nicotinic receptor.</strong> Nature 557: 261-265, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29720657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29720657</a>] [<a href="https://doi.org/10.1038/s41586-018-0081-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29720657">Walsh et al. (2018)</a> used cryoelectron microscopy to obtain structures for the alpha-4 (CHRNA4; <a href="/entry/118504">118504</a>)-beta-2 nicotinic acetylcholine receptor in both the 2-alpha-to-3-beta and 3-alpha-to-2-beta stoichiometries from a single sample. The antibody fragments specific to beta-2 were used to break symmetry during particle alignment and to obtain high-resolution reconstructions of receptors of both stoichiometries in complex with nicotine. The results revealed principles of subunit assembly and the structural basis of the distinctive biophysical and pharmacologic properties of the 2 different stoichiometries of this receptor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29720657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic Southern analysis of hamster/human somatic cell hybrid DNAs, <a href="#2" class="mim-tip-reference" title="Anand, R., Lindstrom, J. <strong>Chromosomal localization of seven neuronal nicotinic acetylcholine receptor subunit genes in humans.</strong> Genomics 13: 962-967, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1505988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1505988</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90008-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1505988">Anand and Lindstrom (1992)</a> mapped the gene encoding the beta-2 subunit of the human neuronal nicotinic acetylcholine receptor to chromosome 1. The corresponding gene is located on chromosome 3 in the mouse (<a href="#3" class="mim-tip-reference" title="Bessis, A., Simon-Chazottes, D., Devillers-Thiery, A., Guenet, J.-L., Changeux, J.-P. <strong>Chromosomal localization of the mouse genes coding for alpha-2, alpha-3, alpha-4 and beta-2 subunits of neuronal nicotinic acetylcholine receptor.</strong> FEBS Lett. 264: 48-52, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2338144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2338144</a>] [<a href="https://doi.org/10.1016/0014-5793(90)80761-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2338144">Bessis et al., 1990</a>). By fluorescence in situ hybridization, <a href="#16" class="mim-tip-reference" title="Rempel, N., Heyers, S., Engels, H., Sleegers, E., Steinlein, O. K. <strong>The structures of the human neuronal nicotinic acetylcholine receptor beta-2- and alpha-3-subunit genes (CHRNB2 and CHRNA3).</strong> Hum. Genet. 103: 645-653, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921897</a>] [<a href="https://doi.org/10.1007/s004390050885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921897">Rempel et al. (1998)</a> narrowed the chromosomal assignment of the CHRNB2 gene to 1q21. <a href="#10" class="mim-tip-reference" title="Lueders, K. K., Elliott, R. W., Marenholz, I., Mischke, D., DuPree, M., Hamer, D. <strong>Genomic organization and mapping of the human and mouse neuronal beta-1-nicotinic acetylcholine receptor genes.</strong> Mammalian Genome 10: 900-905, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441742</a>] [<a href="https://doi.org/10.1007/s003359901111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441742">Lueders et al. (1999)</a> mapped the CHRNB2 gene to 1q21.3 by the finding of its sequence within a YAC contig. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10441742+1505988+9921897+2338144" 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>Clustered attacks of epileptic episodes originating from the frontal lobe during sleep represent the main manifestation of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE, ENFL; <a href="/entry/600513">600513</a>). Because of the description of mutations in the CHRNA4 gene, encoding the alpha-4 subunit of the neuronal nicotinic acetylcholine receptor, in a patient with autosomal dominant nocturnal frontal lobe epilepsy, <a href="#16" class="mim-tip-reference" title="Rempel, N., Heyers, S., Engels, H., Sleegers, E., Steinlein, O. K. <strong>The structures of the human neuronal nicotinic acetylcholine receptor beta-2- and alpha-3-subunit genes (CHRNB2 and CHRNA3).</strong> Hum. Genet. 103: 645-653, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921897</a>] [<a href="https://doi.org/10.1007/s004390050885" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921897">Rempel et al. (1998)</a> were prompted to consider other members of the neuronal nicotinic acetylcholine receptor family as candidates for the same disorder in families that did not link to CHRNA4 and for other idiopathic epilepsies. They found no mutations in the CHRNB2 gene among 8 unrelated patients with a history of nocturnal frontal lobe epilepsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921897" 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>Because of the location of the CHRNB2 gene in the region of chromosome 1 where a form of ENFL maps (ENFL3; <a href="/entry/605375">605375</a>), <a href="#5" class="mim-tip-reference" title="De Fusco, M., Becchetti, A., Patrignani, A., Annesi, G., Gambardella, A., Quattrone, A., Ballabio, A., Wanke, E., Casari, G. <strong>The nicotinic receptor beta-2 subunit is mutant in nocturnal frontal lobe epilepsy.</strong> Nature Genet. 26: 275-276, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11062464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11062464</a>] [<a href="https://doi.org/10.1038/81566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11062464">De Fusco et al. (2000)</a> sequenced the entire coding region of the gene in patients and found a missense mutation, val287 to leu (V287L; <a href="#0001">118507.0001</a>). All affected members of the family and 4 phenotypically normal individuals shared the heterozygous aberrant band, thus confirming the incomplete penetrance (approximately 75%) previously reported in ENFL pedigrees. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11062464" 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="Phillips, H. A., Favre, I., Kirkpatrick, M., Zuberi, S. M., Goudie, D., Heron, S. E., Scheffer, I. E., Sutherland, G. R., Berkovic, S. F., Bertrand, D., Mulley, J. C. <strong>CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy.</strong> Am. J. Hum. Genet. 68: 225-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11104662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11104662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11104662[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316946" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11104662">Phillips et al. (2001)</a> described a mutation in the CHRNB2 gene in a Scottish family with ENFL3 (<a href="#0002">118507.0002</a>); the mutation resulted in a different amino acid substitution at the same valine site affected in the family reported by <a href="#5" class="mim-tip-reference" title="De Fusco, M., Becchetti, A., Patrignani, A., Annesi, G., Gambardella, A., Quattrone, A., Ballabio, A., Wanke, E., Casari, G. <strong>The nicotinic receptor beta-2 subunit is mutant in nocturnal frontal lobe epilepsy.</strong> Nature Genet. 26: 275-276, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11062464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11062464</a>] [<a href="https://doi.org/10.1038/81566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11062464">De Fusco et al. (2000)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11104662+11062464" 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="#15" class="mim-tip-reference" title="Picciotto, M. R., Zoli, M., Lena, C., Bessis, A., Lallemand, Y., LeNovere, N., Vincent, P., Pich, E. M., Brulet, P., Changeux, J.-P. <strong>Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain.</strong> Nature 374: 65-67, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7870173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7870173</a>] [<a href="https://doi.org/10.1038/374065a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7870173">Picciotto et al. (1995)</a> disrupted the CHRNB2 mouse homolog in embryonic stem (ES) cells to generate 'knockout' mice deficient in this subunit. Homozygous mice were viable, mated normally, and showed no obvious physical deficits. However, their brains showed absence of high-affinity binding sites for nicotine, and electrophysiologic recordings from brain slices showed that thalamic neurons did not respond to nicotine application. Furthermore, behavioral tests demonstrated that nicotine no longer augmented the performance of the deficient mice on passive avoidance, a test of associative memory. Paradoxically, mutant mice were able to perform better than their nonmutant sibs on this task. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7870173" 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="#19" class="mim-tip-reference" title="Zoli, M., Picciotto, M. R., Ferrari, R., Cocchi, D., Changeux, J.-P. <strong>Increased neurodegeneration during ageing in mice lacking high-affinity nicotine receptors.</strong> EMBO J. 18: 1235-1244, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10064590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10064590</a>] [<a href="https://doi.org/10.1093/emboj/18.5.1235" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10064590">Zoli et al. (1999)</a> demonstrated increased age-related neurodegeneration in the beta-2 knockout mice generated by <a href="#15" class="mim-tip-reference" title="Picciotto, M. R., Zoli, M., Lena, C., Bessis, A., Lallemand, Y., LeNovere, N., Vincent, P., Pich, E. M., Brulet, P., Changeux, J.-P. <strong>Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain.</strong> Nature 374: 65-67, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7870173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7870173</a>] [<a href="https://doi.org/10.1038/374065a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7870173">Picciotto et al. (1995)</a>. Neuronal hypotrophy, astrogliosis, and microgliosis were limited to specific anatomic regions including CA1 and CA3 fields in the hippocampus and neocortical areas but not the dentate gyrus or the thalamus. The pattern of neuronal atrophy and gliosis corresponded to areas previously shown to be vulnerable to normal aging but did not correspond simply to the pattern of distribution of beta-2 subunits. There were no significant alterations of other cholinergic markers such as acetylcholinesterase, choline transporters, alpha-bungarotoxin binding sites or muscarinic acetylcholine receptors. There was an increase in the level of circulating corticosterone. The authors proposed that the loss of neurons in the CA3 field could be both a cause and an effect of elevated levels of corticosteroids. Older knockout mice were defective in spatial learning tasks, whereas younger knockout mice performed normally. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10064590+7870173" 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="Marubio, L. M., del Mar Arroyo-Jimenez, M., Cordero-Erausquin, M., Lena, C., Le Novere, N., de Kerchove d'Exaerde, A., Huchet, M., Damaj, M. I., Changeux, J.-P. <strong>Reduced antinociception in mice lacking neuronal nicotinic receptor subunits.</strong> Nature 398: 805-810, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10235262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10235262</a>] [<a href="https://doi.org/10.1038/19756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10235262">Marubio et al. (1999)</a> disrupted the alpha-4 subunit of the neuronal nicotinic acetylcholine receptor by homologous recombination and studied homozygous alpha-4-null mice and mice lacking the beta-2 subunit of the nAChR. The homozygous alpha-4 -/- mice no longer expressed high-affinity nicotine binding sites throughout the brain. In addition, both types of mutant mice displayed a reduced antinociceptive effect of nicotine on the hot-plate test and diminished sensitivity to nicotine in the tail-flick test. Patch-clamp recordings revealed that raphe magnus and thalamic neurons no longer responded to nicotine. <a href="#12" class="mim-tip-reference" title="Marubio, L. M., del Mar Arroyo-Jimenez, M., Cordero-Erausquin, M., Lena, C., Le Novere, N., de Kerchove d'Exaerde, A., Huchet, M., Damaj, M. I., Changeux, J.-P. <strong>Reduced antinociception in mice lacking neuronal nicotinic receptor subunits.</strong> Nature 398: 805-810, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10235262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10235262</a>] [<a href="https://doi.org/10.1038/19756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10235262">Marubio et al. (1999)</a> stated that the alpha-4 nAChR subunit, thought to associate with the beta-2 nAChR subunit, is therefore crucial for nicotine-elicited antinociception. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10235262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Manfredi, I., Zani, A. D., Rampoldi, L., Pegorini, S., Bernascone, I., Moretti, M., Gotti, C., Croci, L., Consalez, G. G., Ferini-Strambi, L., Sala, M., Pattini, L., Casari, G. <strong>Expression of mutant beta-2 nicotinic receptors during development is crucial for epileptogenesis.</strong> Hum. Molec. Genet. 18: 1075-1088, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19153075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19153075</a>] [<a href="https://doi.org/10.1093/hmg/ddp004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19153075">Manfredi et al. (2009)</a> developed and characterized a mouse model of ENFL3 carrying the V287L mutation (<a href="#0001">118507.0001</a>) of the CHRNB2 gene. Mice expressing mutant receptors showed a spontaneous epileptic phenotype by electroencephalography with very frequent interictal spikes and seizures. Expression of the mutant protein was driven by a neuronal-specific tetracycline-controlled promoter, which allowed reversible planned silencing of transgene expression. Restricted silencing during development was sufficient to prevent the occurrence of epileptic seizures in adulthood. <a href="#11" class="mim-tip-reference" title="Manfredi, I., Zani, A. D., Rampoldi, L., Pegorini, S., Bernascone, I., Moretti, M., Gotti, C., Croci, L., Consalez, G. G., Ferini-Strambi, L., Sala, M., Pattini, L., Casari, G. <strong>Expression of mutant beta-2 nicotinic receptors during development is crucial for epileptogenesis.</strong> Hum. Molec. Genet. 18: 1075-1088, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19153075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19153075</a>] [<a href="https://doi.org/10.1093/hmg/ddp004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19153075">Manfredi et al. (2009)</a> hypothesized that mutant nicotinic receptors are responsible for abnormal formation of neuronal circuits and/or long-lasting alteration of network assembly in the developing brain, thus leading to epilepsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19153075" 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="#9" class="mim-tip-reference" title="Guillem, K., Bloem, B., Poorthuis, R. B., Loos, M., Smit, A. B., Maskos, U., Spijker, S., Mansvelder, H. D. <strong>Nicotinic acetylcholine receptor beta-2 subunits in the medial prefrontal cortex control attention.</strong> Science 333: 888-891, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21836018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21836018</a>] [<a href="https://doi.org/10.1126/science.1207079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21836018">Guillem et al. (2011)</a> found that mice carrying nAChR beta-2-subunit deletions have impaired attention performance. Efficient lentiviral vector-mediated reexpression of functional beta-2-subunit-containing nAChRs in prefrontal cortex neurons of the prelimbic area completely restored the attentional deficient but did not affect impulsive and motivational behavior. <a href="#9" class="mim-tip-reference" title="Guillem, K., Bloem, B., Poorthuis, R. B., Loos, M., Smit, A. B., Maskos, U., Spijker, S., Mansvelder, H. D. <strong>Nicotinic acetylcholine receptor beta-2 subunits in the medial prefrontal cortex control attention.</strong> Science 333: 888-891, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21836018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21836018</a>] [<a href="https://doi.org/10.1126/science.1207079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21836018">Guillem et al. (2011)</a> concluded that beta-2-subunit expression in the prefrontal cortex is sufficient for endogenous nAChR-mediated cholinergic regulation of attentional performance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21836018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs74315291 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315291;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs74315291?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs74315291" 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=rs74315291" 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=RCV000019047 OR RCV004700252" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019047, RCV004700252" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019047...</a>
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<p>In affected members of an Italian family with nocturnal frontal lobe epilepsy-3 (ENFL3; <a href="/entry/605375">605375</a>) reported by <a href="#7" class="mim-tip-reference" title="Gambardella, A., Annesi, G., De Fusco, M., Patrignani, A., Aguglia, U., Annesi, F., Pasqua, A. A., Spadafora, P., Oliveri, R. L., Valentino, P., Zappia, M., Ballabio, A., Casari, G., Quattrone, A. <strong>A new locus for autosomal dominant nocturnal frontal lobe epilepsy maps to chromosome 1.</strong> Neurology 55: 1467-1471, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11094099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11094099</a>] [<a href="https://doi.org/10.1212/wnl.55.10.1467" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11094099">Gambardella et al. (2000)</a>, <a href="#5" class="mim-tip-reference" title="De Fusco, M., Becchetti, A., Patrignani, A., Annesi, G., Gambardella, A., Quattrone, A., Ballabio, A., Wanke, E., Casari, G. <strong>The nicotinic receptor beta-2 subunit is mutant in nocturnal frontal lobe epilepsy.</strong> Nature Genet. 26: 275-276, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11062464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11062464</a>] [<a href="https://doi.org/10.1038/81566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11062464">De Fusco et al. (2000)</a> found a heterozygous G-to-C transversion in exon 5 of the CHRNB2 gene, resulting in a val287-to-leu (V287L) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11094099+11062464" 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 EPILEPSY, NOCTURNAL FRONTAL LOBE, 3</strong>
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CHRNB2, VAL287MET
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs74315291 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315291;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs74315291?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs74315291" 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=rs74315291" 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=RCV000019048 OR RCV001091721 OR RCV001216785 OR RCV003493411 OR RCV004018644" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019048, RCV001091721, RCV001216785, RCV003493411, RCV004018644" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019048...</a>
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<p>In affected members of a Scottish family with nocturnal frontal lobe epilepsy-3 (ENFL3; <a href="/entry/605375">605375</a>), <a href="#14" class="mim-tip-reference" title="Phillips, H. A., Favre, I., Kirkpatrick, M., Zuberi, S. M., Goudie, D., Heron, S. E., Scheffer, I. E., Sutherland, G. R., Berkovic, S. F., Bertrand, D., Mulley, J. C. <strong>CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy.</strong> Am. J. Hum. Genet. 68: 225-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11104662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11104662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11104662[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316946" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11104662">Phillips et al. (2001)</a> identified a heterozygous G-to-A transition at nucleotide 1025 in the CHRNB2 gene, resulting in a val287-to-met (V287M) substitution within the M2 domain. Codon 287 was also involved in the family reported by <a href="#5" class="mim-tip-reference" title="De Fusco, M., Becchetti, A., Patrignani, A., Annesi, G., Gambardella, A., Quattrone, A., Ballabio, A., Wanke, E., Casari, G. <strong>The nicotinic receptor beta-2 subunit is mutant in nocturnal frontal lobe epilepsy.</strong> Nature Genet. 26: 275-276, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11062464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11062464</a>] [<a href="https://doi.org/10.1038/81566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11062464">De Fusco et al. (2000)</a>; see <a href="#0001">118507.0001</a>. The mutation is located in an evolutionarily conserved region of the gene. Functional receptors with the V287M mutation were highly expressed in Xenopus oocytes and characterized by an approximately 10-fold increase in acetylcholine sensitivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11104662+11062464" 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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Anand, R., Lindstrom, J.
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Bessis, A., Simon-Chazottes, D., Devillers-Thiery, A., Guenet, J.-L., Changeux, J.-P.
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<strong>Chromosomal localization of the mouse genes coding for alpha-2, alpha-3, alpha-4 and beta-2 subunits of neuronal nicotinic acetylcholine receptor.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2338144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2338144</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2338144" 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/10.1016/0014-5793(90)80761-7" target="_blank">Full Text</a>]
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Champtiaux, N., Gotti, C., Cordero-Erausquin, M., David, D. J., Przybylski, C., Lena, C., Clementi, F., Moretti, M., Rossi, F. M., Le Novere, N., McIntosh, J. M., Gardier, A. M., Changeux, J.-P.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12944511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12944511</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12944511" 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/10.1523/JNEUROSCI.23-21-07820.2003" target="_blank">Full Text</a>]
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De Fusco, M., Becchetti, A., Patrignani, A., Annesi, G., Gambardella, A., Quattrone, A., Ballabio, A., Wanke, E., Casari, G.
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<strong>The nicotinic receptor beta-2 subunit is mutant in nocturnal frontal lobe epilepsy.</strong>
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Nature Genet. 26: 275-276, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11062464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11062464</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11062464" 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/10.1038/81566" target="_blank">Full Text</a>]
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<strong>Comparative structure of human neuronal alpha(2)-alpha(7) and beta(2)-beta(4) nicotinic acetylcholine receptor subunits and functional expression of the alpha(2), alpha(3), alpha(4), alpha(7), beta(2), and beta(4) subunits.</strong>
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[<a href="https://doi.org/10.1007/BF02736842" target="_blank">Full Text</a>]
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Gambardella, A., Annesi, G., De Fusco, M., Patrignani, A., Aguglia, U., Annesi, F., Pasqua, A. A., Spadafora, P., Oliveri, R. L., Valentino, P., Zappia, M., Ballabio, A., Casari, G., Quattrone, A.
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<strong>A new locus for autosomal dominant nocturnal frontal lobe epilepsy maps to chromosome 1.</strong>
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Neurology 55: 1467-1471, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11094099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11094099</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11094099" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Groot Kormelink, P. J., Luyten, W. H. M. L.
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<strong>Cloning and sequence of full-length cDNAs encoding the human neuronal nicotinic acetylcholine receptor (nAChR) subunits beta-3 and beta-4 and expression of seven nAChR subunits in the human neuroblastoma cell line SH-SY5Y and/or IMR-32.</strong>
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[<a href="https://doi.org/10.1016/s0014-5793(96)01383-x" target="_blank">Full Text</a>]
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Guillem, K., Bloem, B., Poorthuis, R. B., Loos, M., Smit, A. B., Maskos, U., Spijker, S., Mansvelder, H. D.
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<strong>Nicotinic acetylcholine receptor beta-2 subunits in the medial prefrontal cortex control attention.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21836018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21836018</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21836018" 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/10.1126/science.1207079" target="_blank">Full Text</a>]
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<a id="Lueders1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Lueders, K. K., Elliott, R. W., Marenholz, I., Mischke, D., DuPree, M., Hamer, D.
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[<a href="https://doi.org/10.1007/s003359901111" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
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<a id="Manfredi2009" class="mim-anchor"></a>
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Manfredi, I., Zani, A. D., Rampoldi, L., Pegorini, S., Bernascone, I., Moretti, M., Gotti, C., Croci, L., Consalez, G. G., Ferini-Strambi, L., Sala, M., Pattini, L., Casari, G.
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[<a href="https://doi.org/10.1093/hmg/ddp004" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
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<a id="Marubio1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Marubio, L. M., del Mar Arroyo-Jimenez, M., Cordero-Erausquin, M., Lena, C., Le Novere, N., de Kerchove d'Exaerde, A., Huchet, M., Damaj, M. I., Changeux, J.-P.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10235262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10235262</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10235262" 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/10.1038/19756" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Maskos2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Maskos, U., Molles, B. E., Pons, S., Besson, M., Guiard, B. P., Guilloux, J.-P., Evrard, A., Cazala, P., Cormier, A., Mameli-Engvall, M., Dufour, N., Cloez-Tayarani, I., Bemelmans, A.-P., Mallet, J., Gardier, A. M., David, V., Faure, P., Granon, S., Changeux, J.-P.
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<strong>Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors.</strong>
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Nature 436: 103-107, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16001069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16001069</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16001069" 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/nature03694" target="_blank">Full Text</a>]
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<a id="Phillips2001" class="mim-anchor"></a>
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Phillips, H. A., Favre, I., Kirkpatrick, M., Zuberi, S. M., Goudie, D., Heron, S. E., Scheffer, I. E., Sutherland, G. R., Berkovic, S. F., Bertrand, D., Mulley, J. C.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11104662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11104662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11104662[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11104662" 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/10.1086/316946" target="_blank">Full Text</a>]
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<a id="15" class="mim-anchor"></a>
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<a id="Picciotto1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Picciotto, M. R., Zoli, M., Lena, C., Bessis, A., Lallemand, Y., LeNovere, N., Vincent, P., Pich, E. M., Brulet, P., Changeux, J.-P.
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Nature 374: 65-67, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7870173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7870173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7870173" 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/10.1038/374065a0" target="_blank">Full Text</a>]
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<a id="16" class="mim-anchor"></a>
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<a id="Rempel1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Rempel, N., Heyers, S., Engels, H., Sleegers, E., Steinlein, O. K.
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<strong>The structures of the human neuronal nicotinic acetylcholine receptor beta-2- and alpha-3-subunit genes (CHRNB2 and CHRNA3).</strong>
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Hum. Genet. 103: 645-653, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921897</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921897" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s004390050885" target="_blank">Full Text</a>]
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<a id="Walsh2018" class="mim-anchor"></a>
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<div class="">
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Walsh, R. M., Jr., Roh, S.-H., Gharpure, A., Morales-Perez, C. L., Teng, J., Hibbs, R. E.
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<strong>Structural principles of distinct assemblies of the human alpha-4-beta-2 nicotinic receptor.</strong>
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Nature 557: 261-265, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29720657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29720657</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29720657" 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/s41586-018-0081-7" target="_blank">Full Text</a>]
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<a id="18" class="mim-anchor"></a>
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<a id="Xiu2009" class="mim-anchor"></a>
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<div class="">
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Xiu, X., Puskar, N. L., Shanata, J. A. P., Lester, H. A., Dougherty, D. A.
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<strong>Nicotine binding to brain receptors requires a strong cation-pi interaction.</strong>
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Nature 458: 534-537, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19252481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19252481</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19252481[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19252481" 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/nature07768" target="_blank">Full Text</a>]
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<a id="19" class="mim-anchor"></a>
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<a id="Zoli1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zoli, M., Picciotto, M. R., Ferrari, R., Cocchi, D., Changeux, J.-P.
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<strong>Increased neurodegeneration during ageing in mice lacking high-affinity nicotine receptors.</strong>
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EMBO J. 18: 1235-1244, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10064590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10064590</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10064590" 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/10.1093/emboj/18.5.1235" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 09/07/2018
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<div class="row collapse" id="mimCollapseContributors">
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Ada Hamosh - updated : 9/6/2011<br>Patricia A. Hartz - updated : 5/19/2010<br>George E. Tiller - updated : 10/26/2009<br>Ada Hamosh - updated : 4/28/2009<br>Anne M. Stumpf - updated : 8/4/2005<br>Ada Hamosh - updated : 8/3/2005<br>Victor A. McKusick - updated : 1/23/2001<br>Victor A. McKusick - updated : 10/25/2000<br>Ada Hamosh - updated : 5/6/1999<br>Orest Hurko - updated : 3/18/1999<br>Victor A. McKusick - updated : 1/21/1999<br>Rebekah S. Rasooly - updated : 4/30/1998
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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Creation Date:
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<span class="mim-text-font">
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Victor A. McKusick : 8/14/1992
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alopez : 09/07/2018
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carol : 01/11/2017<br>carol : 01/08/2013<br>carol : 3/21/2012<br>alopez : 9/6/2011<br>terry : 9/6/2011<br>mgross : 5/19/2010<br>mgross : 5/19/2010<br>wwang : 11/10/2009<br>terry : 10/26/2009<br>alopez : 5/5/2009<br>terry : 4/28/2009<br>alopez : 10/25/2006<br>alopez : 8/4/2005<br>alopez : 8/4/2005<br>terry : 8/3/2005<br>terry : 3/14/2005<br>carol : 1/24/2001<br>terry : 1/23/2001<br>alopez : 11/1/2000<br>alopez : 10/31/2000<br>terry : 10/25/2000<br>carol : 4/27/2000<br>carol : 4/27/2000<br>alopez : 5/6/1999<br>alopez : 5/6/1999<br>carol : 3/18/1999<br>carol : 2/1/1999<br>terry : 1/21/1999<br>alopez : 4/30/1998<br>carol : 3/19/1995<br>carol : 8/31/1992<br>carol : 8/14/1992
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<span class="mim-font">
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<strong>*</strong> 118507
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<h3>
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<span class="mim-font">
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CHOLINERGIC RECEPTOR, NEURONAL NICOTINIC, BETA POLYPEPTIDE 2; CHRNB2
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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ACETYLCHOLINE RECEPTOR, NEURONAL NICOTINIC, BETA-2 SUBUNIT
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: CHRNB2</em></strong>
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<strong>
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<em>
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Cytogenetic location: 1q21.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:154,567,778-154,580,013 </span>
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</em>
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</strong>
|
|
<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
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<tr class="active">
|
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<th>
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|
Location
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</th>
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<th>
|
|
Phenotype
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</th>
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<th>
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|
Phenotype <br /> MIM number
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</th>
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<th>
|
|
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>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
|
1q21.3
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</span>
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</td>
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<td>
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<span class="mim-font">
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Epilepsy, nocturnal frontal lobe, 3
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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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605375
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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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</span>
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</td>
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<td>
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<span class="mim-font">
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|
3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are thought to be heteropentamers composed of homologous subunits. See 118508 for additional background information on nAChRs.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Anand and Lindstrom (1990) isolated the beta-2 nAChR subunit by screening human fetal brain cDNA libraries with chicken beta-2 as a probe. The predicted 501-amino acid protein has a putative 25-amino acid signal peptide, and is 95% identical to rat beta-2 protein. </p><p>Groot Kormelink and Luyten (1997) also isolated human beta-2 cDNAs from neuroblastoma cell lines and from frontal cortex. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>Rempel et al. (1998) determined that the CHRNB2 gene comprises 6 exons and spans approximately 9 kb of genomic DNA from the ATG start codon to the TGA stop codon. Exon 1 contains the 5-prime untranslated region, the ATG start codon, and parts of the sequence coding for the putative signal peptide. The hydrophobic transmembrane domains I through III are located in the large exon 5. Exon 6 contains the transmembrane domain IV as well as the translation stop codon and the 3-prime untranslated region. The CHRNB2 introns vary in size from 150 bp (intron 2) to 4.5 kb (intron 5). The splicing at the junctions of CHRNB2 introns 2, 3, and 5 occurred between codons (splicing type 0). Introns 1 and 4 were spliced after the first base (splicing type 1) and the second base of the codon (splicing type 2), respectively. </p>
|
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene 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">
|
|
<p>Elliott et al. (1996) demonstrated that human beta-2 encodes a functional receptor when expressed in combination with human alpha-2 (CHRNA2; 118502), alpha-3 (CHRNA3; 118503), or alpha-4 (CHRNA4; 118504) in Xenopus oocytes. </p><p>By immunoprecipitation analysis of mouse striatal extracts, Champtiaux et al. (2003) identified 3 main types of heteromeric nAChRs: alpha-4/beta-2, alpha-6 (CHRNA6; 606888)/beta-2, and alpha-4/alpha-6/beta-2. Alpha-6/beta-2 nAChRs were mainly located on dopamine (DA) nerve terminals and were the direct target of alpha-conotoxin MII inhibition. A combination of alpha-6/beta-2 and alpha-4/beta-2 nAChRs mediated endogenous cholinergic modulation of DA release induced by systemic nicotine administration at nerve terminals. Alpha-4/beta-2 nAChRs appeared to represent the majority of nAChRs on DA neuron soma and contributed to nicotine reinforcement. </p><p>Maskos et al. (2005) reexpressed the beta-2 subunit of the nicotinic acetylcholine receptor by stereotaxically injecting a lentiviral vector into the ventral tegmental area of mice carrying beta-2 subunit deletions. Maskos et al. (2005) demonstrated the efficient reexpression of electrophysiologically responsive, ligand-binding nicotinic acetylcholine receptors in DA-containing neurons of the ventral tegmental area, together with the recovery of nicotine-elicited DA release and nicotine self-administration. Maskos et al. (2005) also quantified exploratory behaviors of the mice, and showed that beta-2 subunit reexpression restored slow exploratory behavior (a measure of cognitive function) to wildtype levels, but did not affect fast navigation behavior. Maskos et al. (2005) concluded that their data demonstrated the sufficient role of the ventral tegmental area in both nicotine reinforcement and endogenous cholinergic regulation of cognitive functions. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Xiu et al. (2009) showed that at the brain acetylcholine receptors alpha-4-beta-2 thought to underlie nicotine addiction, the high affinity for nicotine is the result of a strong cation-pi interaction to a specific aromatic amino acid of the receptor, TrpB. In contrast, the low affinity for nicotine at the muscle-type acetylcholine receptor is largely due to the absence of this key interaction, even though the immediate binding site residues, including the key amino acid TrpB, are identical in the brain and muscle receptors. At the same time a hydrogen bond from nicotine to the backbone carbonyl of TrpB is enhanced in the neuronal receptor relative to the muscle type. A point mutation near TrpB that differentiates alpha-4-beta-2 and muscle-type receptors seems to influence the shape of the binding site, allowing nicotine to interact more strongly with TrpB in the neuronal receptor. </p><p><strong><em>Cryoelectron Microscopy</em></strong></p><p>
|
|
Walsh et al. (2018) used cryoelectron microscopy to obtain structures for the alpha-4 (CHRNA4; 118504)-beta-2 nicotinic acetylcholine receptor in both the 2-alpha-to-3-beta and 3-alpha-to-2-beta stoichiometries from a single sample. The antibody fragments specific to beta-2 were used to break symmetry during particle alignment and to obtain high-resolution reconstructions of receptors of both stoichiometries in complex with nicotine. The results revealed principles of subunit assembly and the structural basis of the distinctive biophysical and pharmacologic properties of the 2 different stoichiometries of this receptor. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By genomic Southern analysis of hamster/human somatic cell hybrid DNAs, Anand and Lindstrom (1992) mapped the gene encoding the beta-2 subunit of the human neuronal nicotinic acetylcholine receptor to chromosome 1. The corresponding gene is located on chromosome 3 in the mouse (Bessis et al., 1990). By fluorescence in situ hybridization, Rempel et al. (1998) narrowed the chromosomal assignment of the CHRNB2 gene to 1q21. Lueders et al. (1999) mapped the CHRNB2 gene to 1q21.3 by the finding of its sequence within a YAC contig. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Clustered attacks of epileptic episodes originating from the frontal lobe during sleep represent the main manifestation of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE, ENFL; 600513). Because of the description of mutations in the CHRNA4 gene, encoding the alpha-4 subunit of the neuronal nicotinic acetylcholine receptor, in a patient with autosomal dominant nocturnal frontal lobe epilepsy, Rempel et al. (1998) were prompted to consider other members of the neuronal nicotinic acetylcholine receptor family as candidates for the same disorder in families that did not link to CHRNA4 and for other idiopathic epilepsies. They found no mutations in the CHRNB2 gene among 8 unrelated patients with a history of nocturnal frontal lobe epilepsy. </p><p>Because of the location of the CHRNB2 gene in the region of chromosome 1 where a form of ENFL maps (ENFL3; 605375), De Fusco et al. (2000) sequenced the entire coding region of the gene in patients and found a missense mutation, val287 to leu (V287L; 118507.0001). All affected members of the family and 4 phenotypically normal individuals shared the heterozygous aberrant band, thus confirming the incomplete penetrance (approximately 75%) previously reported in ENFL pedigrees. </p><p>Phillips et al. (2001) described a mutation in the CHRNB2 gene in a Scottish family with ENFL3 (118507.0002); the mutation resulted in a different amino acid substitution at the same valine site affected in the family reported by De Fusco et al. (2000). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Picciotto et al. (1995) disrupted the CHRNB2 mouse homolog in embryonic stem (ES) cells to generate 'knockout' mice deficient in this subunit. Homozygous mice were viable, mated normally, and showed no obvious physical deficits. However, their brains showed absence of high-affinity binding sites for nicotine, and electrophysiologic recordings from brain slices showed that thalamic neurons did not respond to nicotine application. Furthermore, behavioral tests demonstrated that nicotine no longer augmented the performance of the deficient mice on passive avoidance, a test of associative memory. Paradoxically, mutant mice were able to perform better than their nonmutant sibs on this task. </p><p>Zoli et al. (1999) demonstrated increased age-related neurodegeneration in the beta-2 knockout mice generated by Picciotto et al. (1995). Neuronal hypotrophy, astrogliosis, and microgliosis were limited to specific anatomic regions including CA1 and CA3 fields in the hippocampus and neocortical areas but not the dentate gyrus or the thalamus. The pattern of neuronal atrophy and gliosis corresponded to areas previously shown to be vulnerable to normal aging but did not correspond simply to the pattern of distribution of beta-2 subunits. There were no significant alterations of other cholinergic markers such as acetylcholinesterase, choline transporters, alpha-bungarotoxin binding sites or muscarinic acetylcholine receptors. There was an increase in the level of circulating corticosterone. The authors proposed that the loss of neurons in the CA3 field could be both a cause and an effect of elevated levels of corticosteroids. Older knockout mice were defective in spatial learning tasks, whereas younger knockout mice performed normally. </p><p>Marubio et al. (1999) disrupted the alpha-4 subunit of the neuronal nicotinic acetylcholine receptor by homologous recombination and studied homozygous alpha-4-null mice and mice lacking the beta-2 subunit of the nAChR. The homozygous alpha-4 -/- mice no longer expressed high-affinity nicotine binding sites throughout the brain. In addition, both types of mutant mice displayed a reduced antinociceptive effect of nicotine on the hot-plate test and diminished sensitivity to nicotine in the tail-flick test. Patch-clamp recordings revealed that raphe magnus and thalamic neurons no longer responded to nicotine. Marubio et al. (1999) stated that the alpha-4 nAChR subunit, thought to associate with the beta-2 nAChR subunit, is therefore crucial for nicotine-elicited antinociception. </p><p>Manfredi et al. (2009) developed and characterized a mouse model of ENFL3 carrying the V287L mutation (118507.0001) of the CHRNB2 gene. Mice expressing mutant receptors showed a spontaneous epileptic phenotype by electroencephalography with very frequent interictal spikes and seizures. Expression of the mutant protein was driven by a neuronal-specific tetracycline-controlled promoter, which allowed reversible planned silencing of transgene expression. Restricted silencing during development was sufficient to prevent the occurrence of epileptic seizures in adulthood. Manfredi et al. (2009) hypothesized that mutant nicotinic receptors are responsible for abnormal formation of neuronal circuits and/or long-lasting alteration of network assembly in the developing brain, thus leading to epilepsy. </p><p>Guillem et al. (2011) found that mice carrying nAChR beta-2-subunit deletions have impaired attention performance. Efficient lentiviral vector-mediated reexpression of functional beta-2-subunit-containing nAChRs in prefrontal cortex neurons of the prelimbic area completely restored the attentional deficient but did not affect impulsive and motivational behavior. Guillem et al. (2011) concluded that beta-2-subunit expression in the prefrontal cortex is sufficient for endogenous nAChR-mediated cholinergic regulation of attentional performance. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>2 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
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|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 EPILEPSY, NOCTURNAL FRONTAL LOBE, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHRNB2, VAL287LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs74315291,
|
|
|
|
|
|
gnomAD: rs74315291,
|
|
|
|
|
|
ClinVar: RCV000019047, RCV004700252
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of an Italian family with nocturnal frontal lobe epilepsy-3 (ENFL3; 605375) reported by Gambardella et al. (2000), De Fusco et al. (2000) found a heterozygous G-to-C transversion in exon 5 of the CHRNB2 gene, resulting in a val287-to-leu (V287L) substitution. </p>
|
|
</span>
|
|
</div>
|
|
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|
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|
<div>
|
|
<br />
|
|
</div>
|
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|
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</div>
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|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 EPILEPSY, NOCTURNAL FRONTAL LOBE, 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
CHRNB2, VAL287MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs74315291,
|
|
|
|
|
|
gnomAD: rs74315291,
|
|
|
|
|
|
ClinVar: RCV000019048, RCV001091721, RCV001216785, RCV003493411, RCV004018644
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a Scottish family with nocturnal frontal lobe epilepsy-3 (ENFL3; 605375), Phillips et al. (2001) identified a heterozygous G-to-A transition at nucleotide 1025 in the CHRNB2 gene, resulting in a val287-to-met (V287M) substitution within the M2 domain. Codon 287 was also involved in the family reported by De Fusco et al. (2000); see 118507.0001. The mutation is located in an evolutionarily conserved region of the gene. Functional receptors with the V287M mutation were highly expressed in Xenopus oocytes and characterized by an approximately 10-fold increase in acetylcholine sensitivity. </p>
|
|
</span>
|
|
</div>
|
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Anand, R., Lindstrom, J.
|
|
<strong>Nucleotide sequence of the human nicotinic acetylcholine receptor beta-2 subunit gene.</strong>
|
|
Nucleic Acids Res. 18: 4272, 1990.
|
|
|
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|
|
[PubMed: 2377478]
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|
|
[Full Text: https://doi.org/10.1093/nar/18.14.4272]
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Anand, R., Lindstrom, J.
|
|
<strong>Chromosomal localization of seven neuronal nicotinic acetylcholine receptor subunit genes in humans.</strong>
|
|
Genomics 13: 962-967, 1992.
|
|
|
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|
|
[PubMed: 1505988]
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|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90008-g]
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</p>
|
|
</li>
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|
<li>
|
|
<p class="mim-text-font">
|
|
Bessis, A., Simon-Chazottes, D., Devillers-Thiery, A., Guenet, J.-L., Changeux, J.-P.
|
|
<strong>Chromosomal localization of the mouse genes coding for alpha-2, alpha-3, alpha-4 and beta-2 subunits of neuronal nicotinic acetylcholine receptor.</strong>
|
|
FEBS Lett. 264: 48-52, 1990.
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|
[PubMed: 2338144]
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[Full Text: https://doi.org/10.1016/0014-5793(90)80761-7]
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</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Champtiaux, N., Gotti, C., Cordero-Erausquin, M., David, D. J., Przybylski, C., Lena, C., Clementi, F., Moretti, M., Rossi, F. M., Le Novere, N., McIntosh, J. M., Gardier, A. M., Changeux, J.-P.
|
|
<strong>Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice.</strong>
|
|
J. Neurosci. 23: 7820-7829, 2003.
|
|
|
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|
|
[PubMed: 12944511]
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|
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|
|
[Full Text: https://doi.org/10.1523/JNEUROSCI.23-21-07820.2003]
|
|
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|
</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
De Fusco, M., Becchetti, A., Patrignani, A., Annesi, G., Gambardella, A., Quattrone, A., Ballabio, A., Wanke, E., Casari, G.
|
|
<strong>The nicotinic receptor beta-2 subunit is mutant in nocturnal frontal lobe epilepsy.</strong>
|
|
Nature Genet. 26: 275-276, 2000.
|
|
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|
|
[PubMed: 11062464]
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|
[Full Text: https://doi.org/10.1038/81566]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
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