3166 lines
261 KiB
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3166 lines
261 KiB
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Entry
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- *608961 - TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY M, MEMBER 3; TRPM3
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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">*608961</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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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</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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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608961">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>
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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=ENSG00000083067;t=ENST00000677713" 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=80036" 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=608961" 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=ENSG00000083067;t=ENST00000677713" 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_001007470,NM_001007471,NM_001366141,NM_001366142,NM_001366143,NM_001366144,NM_001366145,NM_001366146,NM_001366147,NM_001366148,NM_001366149,NM_001366150,NM_001366151,NM_001366152,NM_001366153,NM_001366154,NM_020952,NM_024971,NM_206944,NM_206945,NM_206946,NM_206947,NM_206948" 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_001366145" 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=608961" 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=10605&isoform_id=10605_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/TRPM3" 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/10047309,10433044,11993700,27597205,27597207,27597209,27597211,27597213,28626247,28626249,28626251,28626253,28626255,28626257,30141363,34783897,45709181,45935368,54632969,55953096,57997061,63102241,119582909,119582910,119582911,119582912,119582913,119582914,119582915,126631314,127802531,148745752,154091308,154091310,154091312,154091314,154091316,154091318,154091320,322510140,581985920,1480771380,1480771382,1480771384,1480771393,1480771406,1480771435,1480771437,1480771439,1480771460,1480771481,1480771483,1480771494,1480771500,1480771504" 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/Q9HCF6" 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=80036" 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=ENSG00000083067;t=ENST00000677713" 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=TRPM3" 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=TRPM3" 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+80036" 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/TRPM3" 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:80036" 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/80036" 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=chr9&hgg_gene=ENST00000677713.2&hgg_start=70529060&hgg_end=71446971&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:17992" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608961[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=608961[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/TRPM3/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/ENSG00000083067" 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=TRPM3" 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=TRPM3" 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=TRPM3" 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=TRPM3&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/PA38271" 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:17992" 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/FBgn0265194.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:2443101" 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/TRPM3#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:2443101" 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/80036/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=80036" 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=WBGene00001651;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001651 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001795;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001795 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001796;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001796 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-060531-95" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
|
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</a>
|
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</span>
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</span>
|
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=TRPM3&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>
|
|
608961
|
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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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TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY M, MEMBER 3; TRPM3
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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>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
MELASTATIN 2; MLSN2<br />
|
|
LONG TRANSIENT RECEPTOR POTENTIAL CHANNEL 3; LTRPC3<br />
|
|
KIAA1616
|
|
</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>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=TRPM3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TRPM3</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/9/236?start=-3&limit=10&highlight=236">9q21.12-q21.13</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:70529060-71446971&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'})">9:70,529,060-71,446,971</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
|
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|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=620253,620224" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/9/236?start=-3&limit=10&highlight=236">
|
|
9q21.12-q21.13
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Cataract 50 with or without glaucoma
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/620253"> 620253 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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<tr>
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Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<p>TRPM3 belongs to the melastatin (TRPM1; <a href="/entry/603576">603576</a>)-related transient receptor (TRPM) channel family. TRPMs are Ca(2+)-permeable cation channels localized predominantly to the plasma membrane. The structural machinery of TRPM channels includes intracellular N and C termini, 6 transmembrane segments, and a pore region between segments 5 and 6. The N-terminal domain has a conserved region, and the C-terminal domain contains a TRP motif, a coiled-coil region, and, in some TRPM channels, an enzymatic domain. TRPM3, unlike other TRPM channels, is activated by sphingosine (review by <a href="#4" class="mim-tip-reference" title="Farooqi, A. A., Javeed, M. K., Javed, Z., Riaz, A. M., Mukhtar, S., Minhaj, S., Abbas, S., Bhatti, S. <strong>TRPM channels: same ballpark, different players, and different rules in immunogenetics.</strong> Immunogenetics 63: 773-787, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21932052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21932052</a>] [<a href="https://doi.org/10.1007/s00251-011-0570-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21932052">Farooqi et al., 2011</a>). TRPM3 is activated by heat and is highly expressed in nociceptor neurons (summary by <a href="#2" class="mim-tip-reference" title="de Sainte Agathe, J. M., Van-Gils, J., Lasseaux, E., Arveiler, B., Lacombe, D., Pfirrmann, C., Raclet, V., Gaston, L., Plaisant, C., Aupy, J., Trimouille, A. <strong>Confirmation and expansion of the phenotype associated with the recurrent p.Val837Met variant in TRPM3.</strong> Europ. J. Med. Genet. 63: 103942, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32439617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32439617</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.103942" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32439617">de Sainte Agathe et al., 2020</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=32439617+21932052" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using genomic sequence analysis, <a href="#7" class="mim-tip-reference" title="Lee, N., Chen, J., Sun, L., Wu, S., Gray, K. R., Rich, A., Huang, M., Lin, J.-H., Feder, J. N., Janovitz, E. B., Levesque, P. C., Blanar, M. A. <strong>Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3).</strong> J. Biol. Chem. 278: 20890-20897, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12672827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12672827</a>] [<a href="https://doi.org/10.1074/jbc.M211232200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12672827">Lee et al. (2003)</a> identified TRPM3 based on its homology to TRPM1 and subsequently isolated a full-length TRPM3 cDNA from a human kidney library. The TRPM3 gene encodes a predicted 1,555-amino acid protein of approximately 170 kD molecular mass that contains 6 transmembrane domains, an ion transport signature domain, a TRP signature motif (XWKFXR), and a coiled-coil domain. The C-terminal sequence of TRPM3 is nearly identical to KIAA1616, cDNA fragment identified by <a href="#9" class="mim-tip-reference" title="Nagase, T., Kikuno, R., Nakayama, M., Hirosawa, M., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 7: 273-281, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10997877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10997877</a>] [<a href="https://doi.org/10.1093/dnares/7.4.271" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10997877">Nagase et al. (2000)</a>. TRPM3 shows 57% amino acid identity to TRPM1. By PCR analysis of a human kidney cDNA library, <a href="#7" class="mim-tip-reference" title="Lee, N., Chen, J., Sun, L., Wu, S., Gray, K. R., Rich, A., Huang, M., Lin, J.-H., Feder, J. N., Janovitz, E. B., Levesque, P. C., Blanar, M. A. <strong>Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3).</strong> J. Biol. Chem. 278: 20890-20897, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12672827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12672827</a>] [<a href="https://doi.org/10.1074/jbc.M211232200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12672827">Lee et al. (2003)</a> identified 5 additional TRPM3 splice variants. Northern blot analysis and quantitative PCR showed strong expression of an approximately 8-kb TRPM3 transcript in kidney, with weaker expression in brain and testis. In situ hybridization to human kidney showed TRPM3 expression in the cytoplasm of collecting tubular epithelium. Immunofluorescence and confocal microscopy showed that HA-tagged full-length TRPM3 localizes to the plasmalemmal compartment. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12672827+10997877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Grimm, C., Kraft, R., Sauerbruch, S., Schultz, G., Harteneck, C. <strong>Molecular and functional characterization of the melastatin-related cation channel TRPM3.</strong> J. Biol. Chem. 278: 21493-21501, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12672799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12672799</a>] [<a href="https://doi.org/10.1074/jbc.M300945200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12672799">Grimm et al. (2003)</a> isolated a TRPM3 cDNA encoding a predicted 1,325-amino acid isoform of 160 kD molecular mass. Northern blot and RT-PCR analysis showed expression of TRPM3 in kidney, brain, ovary, and pancreas; Western blot analysis showed expression of TRPM3 protein in human and bovine, but not mouse, kidney. Confocal fluorescence microscopy of transiently transfected HEK293 cells showed that TRPM3 localizes to intracellular compartments and regions of the plasma membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12672799" 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="Vriens, J., Owsianik, G., Hofmann, T., Philipp, S. E., Stab, J., Chen, X., Benoit, M., Xue, F., Janssens, A., Kerselaers, S., Oberwinkler, J., Vennekens, R., Gudermann, T., Nilius, B., Voets, T. <strong>TRPM3 is a nociceptor channel involved in the detection of noxious heat.</strong> Neuron 70: 482-494, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21555074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21555074</a>] [<a href="https://doi.org/10.1016/j.neuron.2011.02.051" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21555074">Vriens et al. (2011)</a> found expression of the Trpm3 gene in sensory neurons of mouse dorsal root and trigeminal ganglia. The neurosteroid pregnenolone sulfate evoked robust and reversible calcium signals in Trpm3-containing small-diameter neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21555074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using RT-PCR and 5-prime RACE, <a href="#1" class="mim-tip-reference" title="Bennett, T. M., Mackay, D. S., Siegfried, C. J., Shiels, A. <strong>Mutation of the melastatin-related cation channel, TRPM3, underlies inherited cataract and glaucoma.</strong> PLoS One 9: e104000, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25090642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25090642</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25090642[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/10.1371/journal.pone.0104000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25090642">Bennett et al. (2014)</a> analyzed postmortem lens RNA and detected strong evidence for multiple TRPM reference transcripts, including transcript variant 9, which encodes protein isoform k, as well as isoforms 1 to 8, encoding protein isoforms a to h. In addition, the authors detected abundant levels of a novel transcript variant that substituted exon 1 of variant 9 with an expressed sequence tag (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BM712132" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BM712132</a>) that had previously been found in human lens. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25090642" 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 sequence analysis, <a href="#7" class="mim-tip-reference" title="Lee, N., Chen, J., Sun, L., Wu, S., Gray, K. R., Rich, A., Huang, M., Lin, J.-H., Feder, J. N., Janovitz, E. B., Levesque, P. C., Blanar, M. A. <strong>Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3).</strong> J. Biol. Chem. 278: 20890-20897, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12672827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12672827</a>] [<a href="https://doi.org/10.1074/jbc.M211232200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12672827">Lee et al. (2003)</a> showed that the TRPM3 gene contains 24 exons spanning 311 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12672827" 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="#7" class="mim-tip-reference" title="Lee, N., Chen, J., Sun, L., Wu, S., Gray, K. R., Rich, A., Huang, M., Lin, J.-H., Feder, J. N., Janovitz, E. B., Levesque, P. C., Blanar, M. A. <strong>Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3).</strong> J. Biol. Chem. 278: 20890-20897, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12672827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12672827</a>] [<a href="https://doi.org/10.1074/jbc.M211232200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12672827">Lee et al. (2003)</a> mapped the TRPM3 gene to 9q21.12 by genomic sequence analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12672827" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using transient transfections of full-length TRPM3, <a href="#7" class="mim-tip-reference" title="Lee, N., Chen, J., Sun, L., Wu, S., Gray, K. R., Rich, A., Huang, M., Lin, J.-H., Feder, J. N., Janovitz, E. B., Levesque, P. C., Blanar, M. A. <strong>Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3).</strong> J. Biol. Chem. 278: 20890-20897, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12672827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12672827</a>] [<a href="https://doi.org/10.1074/jbc.M211232200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12672827">Lee et al. (2003)</a> showed that TRPM3 mediates calcium entry, and that this entry is potentiated by calcium store depletion. The TRPM3-mediated calcium entry is inhibited by the nonselective calcium channel blocker lanthanide gadolinium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12672827" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using whole-cell patch-clamp experiments, <a href="#6" class="mim-tip-reference" title="Grimm, C., Kraft, R., Sauerbruch, S., Schultz, G., Harteneck, C. <strong>Molecular and functional characterization of the melastatin-related cation channel TRPM3.</strong> J. Biol. Chem. 278: 21493-21501, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12672799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12672799</a>] [<a href="https://doi.org/10.1074/jbc.M300945200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12672799">Grimm et al. (2003)</a> showed constitutively activated cation currents in TRPM3-expressing cells. Cell-attached patch experiments showed spontaneous inward and outward currents in TRPM3-transfected cells. IN fluorescence quench experiments, <a href="#6" class="mim-tip-reference" title="Grimm, C., Kraft, R., Sauerbruch, S., Schultz, G., Harteneck, C. <strong>Molecular and functional characterization of the melastatin-related cation channel TRPM3.</strong> J. Biol. Chem. 278: 21493-21501, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12672799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12672799</a>] [<a href="https://doi.org/10.1074/jbc.M300945200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12672799">Grimm et al. (2003)</a> observed that extracellular hypotonic conditions increased TRPM3-mediated calcium entry and caused cellular swelling. The authors suggested that these results indicated volume-regulated activity for TRPM3 consistent with a role in renal calcium homeostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12672799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Neurodevelopmental Disorder with Hypotonia, Dysmorphic Facies, and Skeletal Anomalies, with or without Seizures</em></strong></p><p>
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By trio-based exome sequencing in 7 unrelated patients with neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures (NEDFSS; <a href="/entry/620224">620224</a>), <a href="#3" class="mim-tip-reference" title="Dyment, D. A., Terhal, P. A., Rustad, C. F., Tveten, K., Griffith, C., Jayakar, P., Shinawi, M., Ellingwood, S., Smith, R., van Gassen, K., McWalter, K., Innes, A. M., Lines, M. A. <strong>De novo substitutions of TRPM3 cause intellectual disability and epilepsy.</strong> Europ. J. Hum. Genet. 27: 1611-1618, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31278393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31278393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31278393[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/s41431-019-0462-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31278393">Dyment et al. (2019)</a> identified a recurrent de novo heterozygous missense mutation in the TRPM3 gene (V837M; <a href="#0001">608961.0001</a>). The mutation, which occurred in the highly conserved S4-S5 linker region of one of several reported protein isoforms, was not present in the gnomAD database. The substitution was proposed to produce a conformational change during gated channel opening and thus have functional significance. Functional studies of the variant and studies of patient cells were not performed. <a href="#3" class="mim-tip-reference" title="Dyment, D. A., Terhal, P. A., Rustad, C. F., Tveten, K., Griffith, C., Jayakar, P., Shinawi, M., Ellingwood, S., Smith, R., van Gassen, K., McWalter, K., Innes, A. M., Lines, M. A. <strong>De novo substitutions of TRPM3 cause intellectual disability and epilepsy.</strong> Europ. J. Hum. Genet. 27: 1611-1618, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31278393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31278393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31278393[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/s41431-019-0462-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31278393">Dyment et al. (2019)</a> also reported an 8-year-old girl (patient 8) with a similar disorder who carried a de novo heterozygous P937Q variant in the TRPM3 gene that was found once in the gnomAD database (frequency of 3.98 x 10(-6)). Patient 8 also carried a de novo heterozygous splice site variant in the DDB1 gene (<a href="/entry/600045">600045</a>) that was considered a variant of uncertain significance; de novo heterozygous mutations in the DDB1 gene cause a different neurodevelopmental disorder (<a href="/entry/619426">619426</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31278393" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 5-year-old French girl with NEDFSS, <a href="#2" class="mim-tip-reference" title="de Sainte Agathe, J. M., Van-Gils, J., Lasseaux, E., Arveiler, B., Lacombe, D., Pfirrmann, C., Raclet, V., Gaston, L., Plaisant, C., Aupy, J., Trimouille, A. <strong>Confirmation and expansion of the phenotype associated with the recurrent p.Val837Met variant in TRPM3.</strong> Europ. J. Med. Genet. 63: 103942, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32439617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32439617</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.103942" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32439617">De Sainte Agathe et al. (2020)</a> identified the recurrent de novo heterozygous V837M mutation in the TRPM3 gene through trio-based whole-exome sequencing. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32439617" 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 trio-based whole-exome sequencing of a 7-year-old boy with NEDFSS, <a href="#5" class="mim-tip-reference" title="Gauthier, L. W., Chatron, N., Cabet, S., Labalme, A., Carneiro, M., Poirot, I., Delvert, C., Gleizal, A., Lesca, G., Putoux, A. <strong>Description of a novel patient with the TRPM3 recurrent p.Val837Met variant.</strong> Europ. J. Med. Genet. 64: 104320, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34438093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34438093</a>] [<a href="https://doi.org/10.1016/j.ejmg.2021.104320" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34438093">Gauthier et al. (2021)</a> identified the de novo recurrent V837M mutation in the TRPM3 gene. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34438093" 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="Lines, M. A., Goldenberg, P., Wong, A., Srivastava, S., Bayat, A., Hove, H., Karstensen, H. G., Anyane-Yeboa, K., Liao, J., Jiang, N., May, A., Guzman, E., and 20 others. <strong>Phenotypic spectrum of the recurrent TRPM3 p.(Val837Met) substitution in seven individuals with global developmental delay and hypotonia.</strong> Am. J. Med. Genet. 188A: 1667-1675, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35146895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35146895</a>] [<a href="https://doi.org/10.1002/ajmg.a.62673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35146895">Lines et al. (2022)</a> identified the recurrent de novo heterozygous V837M mutation in 7 additional unrelated patients with NEDFSS identified through exome sequencing. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35146895" 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>Cataract 50 with or without Glaucoma</em></strong></p><p>
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In affected members of a large 5-generation family segregating autosomal dominant cataract with or without glaucoma mapped to chromosome 9q (CTRCT50; <a href="/entry/620253">620253</a>), <a href="#1" class="mim-tip-reference" title="Bennett, T. M., Mackay, D. S., Siegfried, C. J., Shiels, A. <strong>Mutation of the melastatin-related cation channel, TRPM3, underlies inherited cataract and glaucoma.</strong> PLoS One 9: e104000, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25090642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25090642</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25090642[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/10.1371/journal.pone.0104000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25090642">Bennett et al. (2014)</a> performed exome sequencing and identified a heterozygous missense mutation in the TRPM3 gene (I65M; <a href="#0002">608961.0002</a>) that segregated fully with disease and was not found in controls or public variant databases. In vitro analysis suggested that the mutation introduces an alternative translation start site in TRPM3 transcript variants 1 to 8, resulting in the addition of 89 amino acids to the N-terminal domains of protein isoforms a to h. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25090642" 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>Variant Function</em></strong></p><p>
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<a href="#13" class="mim-tip-reference" title="Zhao, S., Yudin, Y., Rohacs, T. <strong>Disease-associated mutations in the human TRPM3 render the channel overactive via two distinct mechanisms.</strong> eLife 9: e55634, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32343227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32343227</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32343227[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/10.7554/eLife.55634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32343227">Zhao et al. (2020)</a> performed in vitro functional expression studies of the V837M mutation (also known as V990M and V992M) and the P937Q variant (also known as P1090Q and P1092Q) in the TRPM3 gene in transfected Xenopus oocytes and HEK293 cells. Both variants resulted in a constitutive gain-of-function effect with a left shift in the calcium concentration both in the basal state and in response to agonists. The slope of the increase in calcium current as a function of temperature was steeper for the mutant channels compared to wildtype. These effects were more pronounced for the V837M variant. Application of the TRPM3 antagonist primidone inhibited calcium signaling evoked by agonists in both wildtype and mutant channels. These data showed that the disease-associated mutations render the TRPM3 channel overactive, possibly via different mechanisms, and the authors postulated that increased neuronal excitability and/or calcium-induced neuronal damage may underlie disease pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32343227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In HEK293 cells, <a href="#10" class="mim-tip-reference" title="Van Hoeymissen, E., Held, K., Nogueira Freitas, A. C., Janssens, A., Voets, T., Vriens, J. <strong>Gain of channel function and modified gating properties in TRPM3 mutants causing intellectual disability and epilepsy.</strong> eLife 9: e57190, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32427099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32427099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32427099[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/10.7554/eLife.57190" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32427099">Van Hoeymissen et al. (2020)</a> found that both TRPM3 variants (V990M and P1090Q) resulted in increased channel current densities compared to wildtype, both in the basal state and when stimulated by agonists. This was associated with a prominent inwardly rectifying current component for V990M. V990M channels also reduced sensitivity to calcium-dependent desensitization. The amplitude for the heat-induced channel response was also larger in cells carrying the variants compared to controls. Primidone application inhibited the currents in wildtype and P1090Q channels, but blocked V990M currents by only 50%. A gain-of-function effect was observed when the variants were coexpressed with wildtype. These findings indicated that the mutations caused altered functional properties of the channel, and the authors hypothesized that increased calcium influx and depolarizing channel activity is the basis of seizure development and neurodevelopmental symptoms in patients carrying these mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32427099" 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="#12" class="mim-tip-reference" title="Vriens, J., Owsianik, G., Hofmann, T., Philipp, S. E., Stab, J., Chen, X., Benoit, M., Xue, F., Janssens, A., Kerselaers, S., Oberwinkler, J., Vennekens, R., Gudermann, T., Nilius, B., Voets, T. <strong>TRPM3 is a nociceptor channel involved in the detection of noxious heat.</strong> Neuron 70: 482-494, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21555074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21555074</a>] [<a href="https://doi.org/10.1016/j.neuron.2011.02.051" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21555074">Vriens et al. (2011)</a> found that Trpm3-null mice showed impaired adverse responses to injection or ingestion of the Trpm3 agonist pregnenolone sulfate (PS) and to noxious thermal heat compared to control mice. In wildtype mice, PS injection in the paw induced strong nocifensive behavior (paw licking and lifting), PS ingestion resulted in aversion to drinking of PS-tainted water, and thermal heat elicited an aversion. Trpm3-null mice had reduced avoidance to PS and to higher temperatures, including thermal hyperalgesia during inflammation. Trpm3-expressing sensory cells showed a robust response to heat, but not to capsaicin; there was a synergistic effect of PS and heat on activation of the Trpm3 channel. Detailed cellular studies on sensory neurons indicated that both Trpv1 (<a href="/entry/602076">602076</a>) and Trpm3 channels contribute to heat responses, but also have independent heat-sensing mechanisms. Overall, the findings identified TRPM3 as a noxious heat sensor in sensory neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21555074" 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="Vandewauw, I., De Clercq, K., Mulier, M., Held, K., Pinto, S., Van Ranst, N., Segal, A., Voet, T., Vennekens, R., Zimmermann, K., Vriens, J., Voets, T. <strong>A TRP channel trio mediates acute noxious heat sensing.</strong> Nature 555: 662-666, 2018. Note: Erratum: Nature 559: e7, 2018. Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29539642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29539642</a>] [<a href="https://doi.org/10.1038/nature26137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29539642">Vandewauw et al. (2018)</a> showed that acute noxious heat sensing in mice depends on a triad of transient receptor potential ion channels: Trpm3, Trpv1, and Trpa1 (<a href="/entry/604775">604775</a>). <a href="#11" class="mim-tip-reference" title="Vandewauw, I., De Clercq, K., Mulier, M., Held, K., Pinto, S., Van Ranst, N., Segal, A., Voet, T., Vennekens, R., Zimmermann, K., Vriens, J., Voets, T. <strong>A TRP channel trio mediates acute noxious heat sensing.</strong> Nature 555: 662-666, 2018. Note: Erratum: Nature 559: e7, 2018. Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29539642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29539642</a>] [<a href="https://doi.org/10.1038/nature26137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29539642">Vandewauw et al. (2018)</a> found that robust somatosensory heat responsiveness at the cellular and behavioral level is observed only if at least 1 of these TRP channels is functional. However, combined genetic or pharmacologic elimination of all 3 channels largely and selectively prevents heat responses in both isolated sensory neurons and rapidly firing C and A-delta sensory nerve fibers that innervate the skin. Strikingly, Trpv1-/-Trpm3-/-Trpa1-/- triple-knockout mice lack the acute withdrawal response to noxious heat that is necessary to avoid burn injury, while showing normal nociceptive responses to cold or mechanical stimuli and a preserved preference for moderate temperatures. <a href="#11" class="mim-tip-reference" title="Vandewauw, I., De Clercq, K., Mulier, M., Held, K., Pinto, S., Van Ranst, N., Segal, A., Voet, T., Vennekens, R., Zimmermann, K., Vriens, J., Voets, T. <strong>A TRP channel trio mediates acute noxious heat sensing.</strong> Nature 555: 662-666, 2018. Note: Erratum: Nature 559: e7, 2018. Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29539642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29539642</a>] [<a href="https://doi.org/10.1038/nature26137" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29539642">Vandewauw et al. (2018)</a> concluded their findings indicated that the initiation of the acute heat-evoked pain response in sensory nerve endings relies on 3 functionally redundant TRP channels, representing a fault-tolerant mechanism to avoid burn injury. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29539642" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using CRISPR/Cas9 gene editing technology, <a href="#14" class="mim-tip-reference" title="Zhou, Y., Bennett, T. M., Shiels, A. <strong>Mutation of the TRPM3 cation channel underlies progressive cataract development and lens calcification associated with pro-fibrotic and immune cell responses.</strong> FASEB J. 35: e21288, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33484482/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33484482</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33484482[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/10.1096/fj.202002037R" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33484482">Zhou et al. (2021)</a> generated knock-in mice with the TRPM3 cataract-associated I65M mutation (<a href="#0002">608961.0002</a>) and compared them to Trpm3-null mice, noting that the null mice exhibited only mild impairment of lens growth, whereas Trpm3 M/M homozygotes developed severe progressive anterior pyramid-like cataract with microphthalmia. In addition, heterozygous Trpm3 I/M and hemizygous Trpm3 M/- mutants developed anterior pyramidal cataract with delayed onset, consistent with a semidominant lens phenotype. Histochemical staining revealed abnormal accumulation of calcium phosphate-like deposits and collagen fibrils in Trpm3-mutant lenses, and immunoblotting detected increased alpha-II-spectrin (SPTAN1; <a href="/entry/182810">182810</a>) cleavage products consistent with calpain (see <a href="/entry/114220">114220</a>) hyperactivation. Immunofluorescence confocal microscopy of Trpm3-M/M mutant lenses revealed fiber cell membrane degeneration that was accompanied by accumulation of alpha-smooth muscle actin (see <a href="/entry/102620">102620</a>)-positive myofibroblast-like cells and macrosialin (CD68; <a href="/entry/153634">153634</a>)-positive macrophage-like cells. The authors concluded that Trpm3 deficiency impairs lens growth but not lens transparency, and that Trpm3 dysfunction results in progressive lens degeneration and calcification, coupled with profibrotic and immune cell responses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33484482" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=608961[MIM]" class="btn btn-default mim-tip-hint" role="button" 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>
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<p>By trio-based exome sequencing in 7 unrelated patients with neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures (NEDFSS; <a href="/entry/620224">620224</a>), <a href="#3" class="mim-tip-reference" title="Dyment, D. A., Terhal, P. A., Rustad, C. F., Tveten, K., Griffith, C., Jayakar, P., Shinawi, M., Ellingwood, S., Smith, R., van Gassen, K., McWalter, K., Innes, A. M., Lines, M. A. <strong>De novo substitutions of TRPM3 cause intellectual disability and epilepsy.</strong> Europ. J. Hum. Genet. 27: 1611-1618, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31278393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31278393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31278393[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/s41431-019-0462-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31278393">Dyment et al. (2019)</a> identified a de novo heterozygous c.2509G-A transition (c.2509G-A, NM_020952.4) in the TRPM3 gene, resulting in a val837-to-met (V837M) substitution in the highly conserved S4-S5 linker region of one of several reported protein isoforms. The mutation was not present in the gnomAD database. The substitution is proposed to produce a conformational change during gated channel opening and thus have functional significance. Functional studies of the variant and studies of patient cells were not performed. The patients, who were ascertained through the GeneMatcher database, ranged in age from 6 to 38 years. From infancy, they showed poor overall growth with global developmental delay, hypotonia, delayed walking by around 5 years (2 patients were nonambulatory), moderately to severely impaired intellectual development with poor or absent speech, and lack of toilet training. All had epilepsy and/or various types of seizures confirmed by EEG with onset in early childhood. Dysmorphic craniofacial features included broad forehead, deep-set eyes, bulbous nasal tip, long nose, short or long philtrum, and micrognathia. Other more variable features included scoliosis, strabismus, cryptorchidism, foot or finger deformities, and abnormal movements. Brain imaging showed cortical atrophy/enlarged ventricles in 2 patients, but was normal in the other patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31278393" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 5-year-old French girl with NEDFSS, <a href="#2" class="mim-tip-reference" title="de Sainte Agathe, J. M., Van-Gils, J., Lasseaux, E., Arveiler, B., Lacombe, D., Pfirrmann, C., Raclet, V., Gaston, L., Plaisant, C., Aupy, J., Trimouille, A. <strong>Confirmation and expansion of the phenotype associated with the recurrent p.Val837Met variant in TRPM3.</strong> Europ. J. Med. Genet. 63: 103942, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32439617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32439617</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.103942" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32439617">De Sainte Agathe et al. (2020)</a> identified the recurrent de novo heterozygous V837M mutation in the TRPM3 gene through trio-based whole-exome sequencing. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32439617" 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 trio-based whole-exome sequencing of a 7-year-old boy with NEDFSS, <a href="#5" class="mim-tip-reference" title="Gauthier, L. W., Chatron, N., Cabet, S., Labalme, A., Carneiro, M., Poirot, I., Delvert, C., Gleizal, A., Lesca, G., Putoux, A. <strong>Description of a novel patient with the TRPM3 recurrent p.Val837Met variant.</strong> Europ. J. Med. Genet. 64: 104320, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34438093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34438093</a>] [<a href="https://doi.org/10.1016/j.ejmg.2021.104320" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34438093">Gauthier et al. (2021)</a> identified the de novo recurrent V837M mutation in the TRPM3 gene. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34438093" 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="Lines, M. A., Goldenberg, P., Wong, A., Srivastava, S., Bayat, A., Hove, H., Karstensen, H. G., Anyane-Yeboa, K., Liao, J., Jiang, N., May, A., Guzman, E., and 20 others. <strong>Phenotypic spectrum of the recurrent TRPM3 p.(Val837Met) substitution in seven individuals with global developmental delay and hypotonia.</strong> Am. J. Med. Genet. 188A: 1667-1675, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35146895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35146895</a>] [<a href="https://doi.org/10.1002/ajmg.a.62673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35146895">Lines et al. (2022)</a> identified the recurrent de novo heterozygous V837M mutation in 7 additional unrelated patients with NEDFSS identified through exome sequencing. Functional studies of the variant were not performed. The authors noted that clinical seizures were only observed in 2 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35146895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a comment on TRPM3 nomenclature, <a href="#8" class="mim-tip-reference" title="Lines, M. A., Goldenberg, P., Wong, A., Srivastava, S., Bayat, A., Hove, H., Karstensen, H. G., Anyane-Yeboa, K., Liao, J., Jiang, N., May, A., Guzman, E., and 20 others. <strong>Phenotypic spectrum of the recurrent TRPM3 p.(Val837Met) substitution in seven individuals with global developmental delay and hypotonia.</strong> Am. J. Med. Genet. 188A: 1667-1675, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35146895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35146895</a>] [<a href="https://doi.org/10.1002/ajmg.a.62673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35146895">Lines et al. (2022)</a> noted that the V837M mutation in the TRPM3 gene is also known as V990M (c.2986G-A, NM_001007471.2) and V1002M (c.3004G-A, NM_001366145.2). They stated that TRPM3 has over 25 isoforms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35146895" 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>Variant Function</em></strong></p><p>
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<a href="#13" class="mim-tip-reference" title="Zhao, S., Yudin, Y., Rohacs, T. <strong>Disease-associated mutations in the human TRPM3 render the channel overactive via two distinct mechanisms.</strong> eLife 9: e55634, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32343227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32343227</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32343227[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/10.7554/eLife.55634" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32343227">Zhao et al. (2020)</a> performed in vitro functional expression studies of the V837M mutation (also known as V990M and V992M) in transfected Xenopus oocytes and HEK293 cells. The variants resulted in a constitutive gain-of-function effect with a left shift in the calcium concentration both in the basal state and in response to agonists. The slope of the increase in calcium current as a function of temperature was steeper for the mutant channel compared to wildtype. Application of the TRPM3 antagonist primidone inhibited calcium signaling evoked by agonists in both wildtype and mutant channels. These data showed that the disease-associated mutation rendered the TRPM3 channel overactive, possibly via different mechanisms, and the authors postulated that increased neuronal excitability and/or calcium-induced neuronal damage may underlie disease pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32343227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In HEK293 cells, <a href="#10" class="mim-tip-reference" title="Van Hoeymissen, E., Held, K., Nogueira Freitas, A. C., Janssens, A., Voets, T., Vriens, J. <strong>Gain of channel function and modified gating properties in TRPM3 mutants causing intellectual disability and epilepsy.</strong> eLife 9: e57190, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32427099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32427099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32427099[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/10.7554/eLife.57190" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32427099">Van Hoeymissen et al. (2020)</a> found that the TRPM3 variant V990M resulted in increased channel current densities compared to wildtype, both in the basal state and when stimulated by agonists. This was associated with a prominent inwardly rectifying current component for V990M. V990M channels also reduced sensitivity to calcium-dependent desensitization. The amplitude for the heat-induced channel response was also larger in cells carrying the variant compared to controls. Primidone application blocked V990M currents by about 50%. A gain-of-function effect was observed when the variant was were coexpressed with wildtype. These findings indicated that the mutation caused altered functional properties of the channel, and the authors hypothesized that increased calcium influx and depolarizing channel activity is the basis of seizure development and neurodevelopmental symptoms in patients carrying the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32427099" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected members of a large 5-generation family segregating autosomal dominant cataract with or without glaucoma (CTRCT50; <a href="/entry/620253">620253</a>), <a href="#1" class="mim-tip-reference" title="Bennett, T. M., Mackay, D. S., Siegfried, C. J., Shiels, A. <strong>Mutation of the melastatin-related cation channel, TRPM3, underlies inherited cataract and glaucoma.</strong> PLoS One 9: e104000, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25090642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25090642</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25090642[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/10.1371/journal.pone.0104000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25090642">Bennett et al. (2014)</a> identified heterozygosity for a c.195A-G transition in exon 3 of the TRPM3 gene, resulting in an ile65-to-met (I65M) substitution at an evolutionarily conserved residue within a putative calmodulin-binding motif of transcript 9. The variant segregated fully with disease in the family and was not found in 192 unrelated controls or in the 1000 Genomes Project or EVS databases. The authors noted that in a newly identified TRPM3 lens transcript variant, the start codon is located within an expressed sequence tag that replaces exon 1 and the mutation (c.24A-G; I8M) is located in exon 3; however, in transcript variants 1 to 8, in which the start codon is located at the end of exon 4, the mutation is in the 5-prime untranslated region. Transient expression of the mutant sequence in HEK293 cells followed by immunoblot analysis suggested that the mutation introduces an alternative translation start site in TRPM3 transcript variants 1 through 8, resulting in the addition of 89 amino acids to the N-terminal domains of protein isoforms a to h. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25090642" 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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Bennett, T. M., Mackay, D. S., Siegfried, C. J., Shiels, A.
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[<a href="https://doi.org/10.1371/journal.pone.0104000" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ejmg.2020.103942" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/s41431-019-0462-x" target="_blank">Full Text</a>]
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<a id="Farooqi2011" class="mim-anchor"></a>
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Farooqi, A. A., Javeed, M. K., Javed, Z., Riaz, A. M., Mukhtar, S., Minhaj, S., Abbas, S., Bhatti, S.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21932052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21932052</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21932052" 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/s00251-011-0570-4" target="_blank">Full Text</a>]
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<a id="Gauthier2021" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1016/j.ejmg.2021.104320" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1074/jbc.M300945200" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1074/jbc.M211232200" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.62673" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/dnares/7.4.271" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32427099/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32427099</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32427099[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=32427099" 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/10.7554/eLife.57190" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/nature26137" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.neuron.2011.02.051" target="_blank">Full Text</a>]
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<a id="Zhao2020" class="mim-anchor"></a>
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Zhao, S., Yudin, Y., Rohacs, T.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32343227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32343227</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32343227[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=32343227" 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/10.7554/eLife.55634" target="_blank">Full Text</a>]
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<a id="Zhou2021" class="mim-anchor"></a>
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Zhou, Y., Bennett, T. M., Shiels, A.
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<strong>Mutation of the TRPM3 cation channel underlies progressive cataract development and lens calcification associated with pro-fibrotic and immune cell responses.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33484482/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33484482</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33484482[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=33484482" 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/10.1096/fj.202002037R" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 02/17/2023
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Cassandra L. Kniffin - updated : 01/31/2023<br>Cassandra L. Kniffin - updated : 01/21/2020<br>Ada Hamosh - updated : 07/23/2018<br>Cassandra L. Kniffin - updated : 6/11/2012<br>Paul J. Converse - updated : 4/19/2012
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Laura L. Baxter : 10/6/2004
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alopez : 08/02/2023
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carol : 02/20/2023<br>carol : 02/17/2023<br>alopez : 02/06/2023<br>ckniffin : 01/31/2023<br>carol : 02/11/2020<br>carol : 01/22/2020<br>ckniffin : 01/21/2020<br>alopez : 07/23/2018<br>carol : 08/29/2014<br>alopez : 6/19/2012<br>ckniffin : 6/11/2012<br>mgross : 4/25/2012<br>terry : 4/19/2012<br>alopez : 10/6/2004
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<h3>
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<span class="mim-font">
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<strong>*</strong> 608961
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<h3>
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TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY M, MEMBER 3; TRPM3
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</h3>
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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MELASTATIN 2; MLSN2<br />
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LONG TRANSIENT RECEPTOR POTENTIAL CHANNEL 3; LTRPC3<br />
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KIAA1616
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TRPM3</em></strong>
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Cytogenetic location: 9q21.12-q21.13
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Genomic coordinates <span class="small">(GRCh38)</span> : 9:70,529,060-71,446,971 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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9q21.12-q21.13
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<span class="mim-font">
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?Cataract 50 with or without glaucoma
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<span class="mim-font">
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620253
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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<span class="mim-font">
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Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures
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<span class="mim-font">
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620224
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>TRPM3 belongs to the melastatin (TRPM1; 603576)-related transient receptor (TRPM) channel family. TRPMs are Ca(2+)-permeable cation channels localized predominantly to the plasma membrane. The structural machinery of TRPM channels includes intracellular N and C termini, 6 transmembrane segments, and a pore region between segments 5 and 6. The N-terminal domain has a conserved region, and the C-terminal domain contains a TRP motif, a coiled-coil region, and, in some TRPM channels, an enzymatic domain. TRPM3, unlike other TRPM channels, is activated by sphingosine (review by Farooqi et al., 2011). TRPM3 is activated by heat and is highly expressed in nociceptor neurons (summary by de Sainte Agathe et al., 2020). </p>
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<strong>Cloning and Expression</strong>
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<p>Using genomic sequence analysis, Lee et al. (2003) identified TRPM3 based on its homology to TRPM1 and subsequently isolated a full-length TRPM3 cDNA from a human kidney library. The TRPM3 gene encodes a predicted 1,555-amino acid protein of approximately 170 kD molecular mass that contains 6 transmembrane domains, an ion transport signature domain, a TRP signature motif (XWKFXR), and a coiled-coil domain. The C-terminal sequence of TRPM3 is nearly identical to KIAA1616, cDNA fragment identified by Nagase et al. (2000). TRPM3 shows 57% amino acid identity to TRPM1. By PCR analysis of a human kidney cDNA library, Lee et al. (2003) identified 5 additional TRPM3 splice variants. Northern blot analysis and quantitative PCR showed strong expression of an approximately 8-kb TRPM3 transcript in kidney, with weaker expression in brain and testis. In situ hybridization to human kidney showed TRPM3 expression in the cytoplasm of collecting tubular epithelium. Immunofluorescence and confocal microscopy showed that HA-tagged full-length TRPM3 localizes to the plasmalemmal compartment. </p><p>Grimm et al. (2003) isolated a TRPM3 cDNA encoding a predicted 1,325-amino acid isoform of 160 kD molecular mass. Northern blot and RT-PCR analysis showed expression of TRPM3 in kidney, brain, ovary, and pancreas; Western blot analysis showed expression of TRPM3 protein in human and bovine, but not mouse, kidney. Confocal fluorescence microscopy of transiently transfected HEK293 cells showed that TRPM3 localizes to intracellular compartments and regions of the plasma membrane. </p><p>Vriens et al. (2011) found expression of the Trpm3 gene in sensory neurons of mouse dorsal root and trigeminal ganglia. The neurosteroid pregnenolone sulfate evoked robust and reversible calcium signals in Trpm3-containing small-diameter neurons. </p><p>Using RT-PCR and 5-prime RACE, Bennett et al. (2014) analyzed postmortem lens RNA and detected strong evidence for multiple TRPM reference transcripts, including transcript variant 9, which encodes protein isoform k, as well as isoforms 1 to 8, encoding protein isoforms a to h. In addition, the authors detected abundant levels of a novel transcript variant that substituted exon 1 of variant 9 with an expressed sequence tag (GenBank BM712132) that had previously been found in human lens. </p>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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<span class="mim-text-font">
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<p>By genomic sequence analysis, Lee et al. (2003) showed that the TRPM3 gene contains 24 exons spanning 311 kb. </p>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Lee et al. (2003) mapped the TRPM3 gene to 9q21.12 by genomic sequence analysis. </p>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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<span class="mim-text-font">
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<p>Using transient transfections of full-length TRPM3, Lee et al. (2003) showed that TRPM3 mediates calcium entry, and that this entry is potentiated by calcium store depletion. The TRPM3-mediated calcium entry is inhibited by the nonselective calcium channel blocker lanthanide gadolinium. </p><p>Using whole-cell patch-clamp experiments, Grimm et al. (2003) showed constitutively activated cation currents in TRPM3-expressing cells. Cell-attached patch experiments showed spontaneous inward and outward currents in TRPM3-transfected cells. IN fluorescence quench experiments, Grimm et al. (2003) observed that extracellular hypotonic conditions increased TRPM3-mediated calcium entry and caused cellular swelling. The authors suggested that these results indicated volume-regulated activity for TRPM3 consistent with a role in renal calcium homeostasis. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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<span class="mim-text-font">
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<p><strong><em>Neurodevelopmental Disorder with Hypotonia, Dysmorphic Facies, and Skeletal Anomalies, with or without Seizures</em></strong></p><p>
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By trio-based exome sequencing in 7 unrelated patients with neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures (NEDFSS; 620224), Dyment et al. (2019) identified a recurrent de novo heterozygous missense mutation in the TRPM3 gene (V837M; 608961.0001). The mutation, which occurred in the highly conserved S4-S5 linker region of one of several reported protein isoforms, was not present in the gnomAD database. The substitution was proposed to produce a conformational change during gated channel opening and thus have functional significance. Functional studies of the variant and studies of patient cells were not performed. Dyment et al. (2019) also reported an 8-year-old girl (patient 8) with a similar disorder who carried a de novo heterozygous P937Q variant in the TRPM3 gene that was found once in the gnomAD database (frequency of 3.98 x 10(-6)). Patient 8 also carried a de novo heterozygous splice site variant in the DDB1 gene (600045) that was considered a variant of uncertain significance; de novo heterozygous mutations in the DDB1 gene cause a different neurodevelopmental disorder (619426). </p><p>In a 5-year-old French girl with NEDFSS, De Sainte Agathe et al. (2020) identified the recurrent de novo heterozygous V837M mutation in the TRPM3 gene through trio-based whole-exome sequencing. Functional studies were not performed. </p><p>By trio-based whole-exome sequencing of a 7-year-old boy with NEDFSS, Gauthier et al. (2021) identified the de novo recurrent V837M mutation in the TRPM3 gene. Functional studies of the variant were not performed. </p><p>Lines et al. (2022) identified the recurrent de novo heterozygous V837M mutation in 7 additional unrelated patients with NEDFSS identified through exome sequencing. Functional studies of the variant were not performed. </p><p><strong><em>Cataract 50 with or without Glaucoma</em></strong></p><p>
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In affected members of a large 5-generation family segregating autosomal dominant cataract with or without glaucoma mapped to chromosome 9q (CTRCT50; 620253), Bennett et al. (2014) performed exome sequencing and identified a heterozygous missense mutation in the TRPM3 gene (I65M; 608961.0002) that segregated fully with disease and was not found in controls or public variant databases. In vitro analysis suggested that the mutation introduces an alternative translation start site in TRPM3 transcript variants 1 to 8, resulting in the addition of 89 amino acids to the N-terminal domains of protein isoforms a to h. </p><p><strong><em>Variant Function</em></strong></p><p>
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Zhao et al. (2020) performed in vitro functional expression studies of the V837M mutation (also known as V990M and V992M) and the P937Q variant (also known as P1090Q and P1092Q) in the TRPM3 gene in transfected Xenopus oocytes and HEK293 cells. Both variants resulted in a constitutive gain-of-function effect with a left shift in the calcium concentration both in the basal state and in response to agonists. The slope of the increase in calcium current as a function of temperature was steeper for the mutant channels compared to wildtype. These effects were more pronounced for the V837M variant. Application of the TRPM3 antagonist primidone inhibited calcium signaling evoked by agonists in both wildtype and mutant channels. These data showed that the disease-associated mutations render the TRPM3 channel overactive, possibly via different mechanisms, and the authors postulated that increased neuronal excitability and/or calcium-induced neuronal damage may underlie disease pathogenesis. </p><p>In HEK293 cells, Van Hoeymissen et al. (2020) found that both TRPM3 variants (V990M and P1090Q) resulted in increased channel current densities compared to wildtype, both in the basal state and when stimulated by agonists. This was associated with a prominent inwardly rectifying current component for V990M. V990M channels also reduced sensitivity to calcium-dependent desensitization. The amplitude for the heat-induced channel response was also larger in cells carrying the variants compared to controls. Primidone application inhibited the currents in wildtype and P1090Q channels, but blocked V990M currents by only 50%. A gain-of-function effect was observed when the variants were coexpressed with wildtype. These findings indicated that the mutations caused altered functional properties of the channel, and the authors hypothesized that increased calcium influx and depolarizing channel activity is the basis of seizure development and neurodevelopmental symptoms in patients carrying these mutations. </p>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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<span class="mim-text-font">
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<p>Vriens et al. (2011) found that Trpm3-null mice showed impaired adverse responses to injection or ingestion of the Trpm3 agonist pregnenolone sulfate (PS) and to noxious thermal heat compared to control mice. In wildtype mice, PS injection in the paw induced strong nocifensive behavior (paw licking and lifting), PS ingestion resulted in aversion to drinking of PS-tainted water, and thermal heat elicited an aversion. Trpm3-null mice had reduced avoidance to PS and to higher temperatures, including thermal hyperalgesia during inflammation. Trpm3-expressing sensory cells showed a robust response to heat, but not to capsaicin; there was a synergistic effect of PS and heat on activation of the Trpm3 channel. Detailed cellular studies on sensory neurons indicated that both Trpv1 (602076) and Trpm3 channels contribute to heat responses, but also have independent heat-sensing mechanisms. Overall, the findings identified TRPM3 as a noxious heat sensor in sensory neurons. </p><p>Vandewauw et al. (2018) showed that acute noxious heat sensing in mice depends on a triad of transient receptor potential ion channels: Trpm3, Trpv1, and Trpa1 (604775). Vandewauw et al. (2018) found that robust somatosensory heat responsiveness at the cellular and behavioral level is observed only if at least 1 of these TRP channels is functional. However, combined genetic or pharmacologic elimination of all 3 channels largely and selectively prevents heat responses in both isolated sensory neurons and rapidly firing C and A-delta sensory nerve fibers that innervate the skin. Strikingly, Trpv1-/-Trpm3-/-Trpa1-/- triple-knockout mice lack the acute withdrawal response to noxious heat that is necessary to avoid burn injury, while showing normal nociceptive responses to cold or mechanical stimuli and a preserved preference for moderate temperatures. Vandewauw et al. (2018) concluded their findings indicated that the initiation of the acute heat-evoked pain response in sensory nerve endings relies on 3 functionally redundant TRP channels, representing a fault-tolerant mechanism to avoid burn injury. </p><p>Using CRISPR/Cas9 gene editing technology, Zhou et al. (2021) generated knock-in mice with the TRPM3 cataract-associated I65M mutation (608961.0002) and compared them to Trpm3-null mice, noting that the null mice exhibited only mild impairment of lens growth, whereas Trpm3 M/M homozygotes developed severe progressive anterior pyramid-like cataract with microphthalmia. In addition, heterozygous Trpm3 I/M and hemizygous Trpm3 M/- mutants developed anterior pyramidal cataract with delayed onset, consistent with a semidominant lens phenotype. Histochemical staining revealed abnormal accumulation of calcium phosphate-like deposits and collagen fibrils in Trpm3-mutant lenses, and immunoblotting detected increased alpha-II-spectrin (SPTAN1; 182810) cleavage products consistent with calpain (see 114220) hyperactivation. Immunofluorescence confocal microscopy of Trpm3-M/M mutant lenses revealed fiber cell membrane degeneration that was accompanied by accumulation of alpha-smooth muscle actin (see 102620)-positive myofibroblast-like cells and macrosialin (CD68; 153634)-positive macrophage-like cells. The authors concluded that Trpm3 deficiency impairs lens growth but not lens transparency, and that Trpm3 dysfunction results in progressive lens degeneration and calcification, coupled with profibrotic and immune cell responses. </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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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>2 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, DYSMORPHIC FACIES, AND SKELETAL ANOMALIES, WITH OR WITHOUT SEIZURES</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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TRPM3, VAL837MET
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<br />
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SNP: rs1564493599,
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ClinVar: RCV000709842, RCV000766226, RCV001199967, RCV001267689, RCV001809776, RCV002287440, RCV002289990, RCV003148840, RCV004026786
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</span>
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</div>
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<p>By trio-based exome sequencing in 7 unrelated patients with neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures (NEDFSS; 620224), Dyment et al. (2019) identified a de novo heterozygous c.2509G-A transition (c.2509G-A, NM_020952.4) in the TRPM3 gene, resulting in a val837-to-met (V837M) substitution in the highly conserved S4-S5 linker region of one of several reported protein isoforms. The mutation was not present in the gnomAD database. The substitution is proposed to produce a conformational change during gated channel opening and thus have functional significance. Functional studies of the variant and studies of patient cells were not performed. The patients, who were ascertained through the GeneMatcher database, ranged in age from 6 to 38 years. From infancy, they showed poor overall growth with global developmental delay, hypotonia, delayed walking by around 5 years (2 patients were nonambulatory), moderately to severely impaired intellectual development with poor or absent speech, and lack of toilet training. All had epilepsy and/or various types of seizures confirmed by EEG with onset in early childhood. Dysmorphic craniofacial features included broad forehead, deep-set eyes, bulbous nasal tip, long nose, short or long philtrum, and micrognathia. Other more variable features included scoliosis, strabismus, cryptorchidism, foot or finger deformities, and abnormal movements. Brain imaging showed cortical atrophy/enlarged ventricles in 2 patients, but was normal in the other patients. </p><p>In a 5-year-old French girl with NEDFSS, De Sainte Agathe et al. (2020) identified the recurrent de novo heterozygous V837M mutation in the TRPM3 gene through trio-based whole-exome sequencing. Functional studies were not performed. </p><p>By trio-based whole-exome sequencing of a 7-year-old boy with NEDFSS, Gauthier et al. (2021) identified the de novo recurrent V837M mutation in the TRPM3 gene. Functional studies of the variant were not performed. </p><p>Lines et al. (2022) identified the recurrent de novo heterozygous V837M mutation in 7 additional unrelated patients with NEDFSS identified through exome sequencing. Functional studies of the variant were not performed. The authors noted that clinical seizures were only observed in 2 patients. </p><p>In a comment on TRPM3 nomenclature, Lines et al. (2022) noted that the V837M mutation in the TRPM3 gene is also known as V990M (c.2986G-A, NM_001007471.2) and V1002M (c.3004G-A, NM_001366145.2). They stated that TRPM3 has over 25 isoforms. </p><p><strong><em>Variant Function</em></strong></p><p>
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Zhao et al. (2020) performed in vitro functional expression studies of the V837M mutation (also known as V990M and V992M) in transfected Xenopus oocytes and HEK293 cells. The variants resulted in a constitutive gain-of-function effect with a left shift in the calcium concentration both in the basal state and in response to agonists. The slope of the increase in calcium current as a function of temperature was steeper for the mutant channel compared to wildtype. Application of the TRPM3 antagonist primidone inhibited calcium signaling evoked by agonists in both wildtype and mutant channels. These data showed that the disease-associated mutation rendered the TRPM3 channel overactive, possibly via different mechanisms, and the authors postulated that increased neuronal excitability and/or calcium-induced neuronal damage may underlie disease pathogenesis. </p><p>In HEK293 cells, Van Hoeymissen et al. (2020) found that the TRPM3 variant V990M resulted in increased channel current densities compared to wildtype, both in the basal state and when stimulated by agonists. This was associated with a prominent inwardly rectifying current component for V990M. V990M channels also reduced sensitivity to calcium-dependent desensitization. The amplitude for the heat-induced channel response was also larger in cells carrying the variant compared to controls. Primidone application blocked V990M currents by about 50%. A gain-of-function effect was observed when the variant was were coexpressed with wildtype. These findings indicated that the mutation caused altered functional properties of the channel, and the authors hypothesized that increased calcium influx and depolarizing channel activity is the basis of seizure development and neurodevelopmental symptoms in patients carrying the mutation. </p>
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<strong>.0002 CATARACT 50 WITH OR WITHOUT GLAUCOMA (1 family)</strong>
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TRPM3, ILE65MET
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ClinVar: RCV003152306, RCV004719313
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<p>In affected members of a large 5-generation family segregating autosomal dominant cataract with or without glaucoma (CTRCT50; 620253), Bennett et al. (2014) identified heterozygosity for a c.195A-G transition in exon 3 of the TRPM3 gene, resulting in an ile65-to-met (I65M) substitution at an evolutionarily conserved residue within a putative calmodulin-binding motif of transcript 9. The variant segregated fully with disease in the family and was not found in 192 unrelated controls or in the 1000 Genomes Project or EVS databases. The authors noted that in a newly identified TRPM3 lens transcript variant, the start codon is located within an expressed sequence tag that replaces exon 1 and the mutation (c.24A-G; I8M) is located in exon 3; however, in transcript variants 1 to 8, in which the start codon is located at the end of exon 4, the mutation is in the 5-prime untranslated region. Transient expression of the mutant sequence in HEK293 cells followed by immunoblot analysis suggested that the mutation introduces an alternative translation start site in TRPM3 transcript variants 1 through 8, resulting in the addition of 89 amino acids to the N-terminal domains of protein isoforms a to h. </p>
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<strong>REFERENCES</strong>
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<p class="mim-text-font">
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Bennett, T. M., Mackay, D. S., Siegfried, C. J., Shiels, A.
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<strong>Mutation of the melastatin-related cation channel, TRPM3, underlies inherited cataract and glaucoma.</strong>
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PLoS One 9: e104000, 2014.
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[PubMed: 25090642]
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[Full Text: https://doi.org/10.1371/journal.pone.0104000]
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de Sainte Agathe, J. M., Van-Gils, J., Lasseaux, E., Arveiler, B., Lacombe, D., Pfirrmann, C., Raclet, V., Gaston, L., Plaisant, C., Aupy, J., Trimouille, A.
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<strong>Confirmation and expansion of the phenotype associated with the recurrent p.Val837Met variant in TRPM3.</strong>
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Europ. J. Med. Genet. 63: 103942, 2020.
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[PubMed: 32439617]
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[Full Text: https://doi.org/10.1016/j.ejmg.2020.103942]
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<li>
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Dyment, D. A., Terhal, P. A., Rustad, C. F., Tveten, K., Griffith, C., Jayakar, P., Shinawi, M., Ellingwood, S., Smith, R., van Gassen, K., McWalter, K., Innes, A. M., Lines, M. A.
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<strong>De novo substitutions of TRPM3 cause intellectual disability and epilepsy.</strong>
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Europ. J. Hum. Genet. 27: 1611-1618, 2019.
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[PubMed: 31278393]
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[Full Text: https://doi.org/10.1038/s41431-019-0462-x]
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Farooqi, A. A., Javeed, M. K., Javed, Z., Riaz, A. M., Mukhtar, S., Minhaj, S., Abbas, S., Bhatti, S.
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<strong>TRPM channels: same ballpark, different players, and different rules in immunogenetics.</strong>
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Immunogenetics 63: 773-787, 2011.
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[PubMed: 21932052]
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[Full Text: https://doi.org/10.1007/s00251-011-0570-4]
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Gauthier, L. W., Chatron, N., Cabet, S., Labalme, A., Carneiro, M., Poirot, I., Delvert, C., Gleizal, A., Lesca, G., Putoux, A.
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<strong>Description of a novel patient with the TRPM3 recurrent p.Val837Met variant.</strong>
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Europ. J. Med. Genet. 64: 104320, 2021.
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[PubMed: 34438093]
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[Full Text: https://doi.org/10.1016/j.ejmg.2021.104320]
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Grimm, C., Kraft, R., Sauerbruch, S., Schultz, G., Harteneck, C.
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<strong>Molecular and functional characterization of the melastatin-related cation channel TRPM3.</strong>
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J. Biol. Chem. 278: 21493-21501, 2003.
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[PubMed: 12672799]
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[Full Text: https://doi.org/10.1074/jbc.M300945200]
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Lee, N., Chen, J., Sun, L., Wu, S., Gray, K. R., Rich, A., Huang, M., Lin, J.-H., Feder, J. N., Janovitz, E. B., Levesque, P. C., Blanar, M. A.
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<strong>Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3).</strong>
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J. Biol. Chem. 278: 20890-20897, 2003.
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[PubMed: 12672827]
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[Full Text: https://doi.org/10.1074/jbc.M211232200]
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Lines, M. A., Goldenberg, P., Wong, A., Srivastava, S., Bayat, A., Hove, H., Karstensen, H. G., Anyane-Yeboa, K., Liao, J., Jiang, N., May, A., Guzman, E., and 20 others.
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<strong>Phenotypic spectrum of the recurrent TRPM3 p.(Val837Met) substitution in seven individuals with global developmental delay and hypotonia.</strong>
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Am. J. Med. Genet. 188A: 1667-1675, 2022.
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[PubMed: 35146895]
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[Full Text: https://doi.org/10.1002/ajmg.a.62673]
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Nagase, T., Kikuno, R., Nakayama, M., Hirosawa, M., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
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DNA Res. 7: 273-281, 2000.
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[PubMed: 10997877]
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[Full Text: https://doi.org/10.1093/dnares/7.4.271]
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Van Hoeymissen, E., Held, K., Nogueira Freitas, A. C., Janssens, A., Voets, T., Vriens, J.
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<strong>Gain of channel function and modified gating properties in TRPM3 mutants causing intellectual disability and epilepsy.</strong>
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eLife 9: e57190, 2020.
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[PubMed: 32427099]
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[Full Text: https://doi.org/10.7554/eLife.57190]
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Vandewauw, I., De Clercq, K., Mulier, M., Held, K., Pinto, S., Van Ranst, N., Segal, A., Voet, T., Vennekens, R., Zimmermann, K., Vriens, J., Voets, T.
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<strong>A TRP channel trio mediates acute noxious heat sensing.</strong>
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Nature 555: 662-666, 2018. Note: Erratum: Nature 559: e7, 2018. Electronic Article.
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[PubMed: 29539642]
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[Full Text: https://doi.org/10.1038/nature26137]
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Vriens, J., Owsianik, G., Hofmann, T., Philipp, S. E., Stab, J., Chen, X., Benoit, M., Xue, F., Janssens, A., Kerselaers, S., Oberwinkler, J., Vennekens, R., Gudermann, T., Nilius, B., Voets, T.
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<strong>TRPM3 is a nociceptor channel involved in the detection of noxious heat.</strong>
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Neuron 70: 482-494, 2011.
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[PubMed: 21555074]
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[Full Text: https://doi.org/10.1016/j.neuron.2011.02.051]
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Zhao, S., Yudin, Y., Rohacs, T.
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<strong>Disease-associated mutations in the human TRPM3 render the channel overactive via two distinct mechanisms.</strong>
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eLife 9: e55634, 2020.
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[PubMed: 32343227]
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[Full Text: https://doi.org/10.7554/eLife.55634]
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Zhou, Y., Bennett, T. M., Shiels, A.
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<strong>Mutation of the TRPM3 cation channel underlies progressive cataract development and lens calcification associated with pro-fibrotic and immune cell responses.</strong>
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FASEB J. 35: e21288, 2021.
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[PubMed: 33484482]
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[Full Text: https://doi.org/10.1096/fj.202002037R]
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Marla J. F. O'Neill - updated : 02/17/2023<br>Cassandra L. Kniffin - updated : 01/31/2023<br>Cassandra L. Kniffin - updated : 01/21/2020<br>Ada Hamosh - updated : 07/23/2018<br>Cassandra L. Kniffin - updated : 6/11/2012<br>Paul J. Converse - updated : 4/19/2012
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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