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Entry
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- *605145 - ANKH INORGANIC PYROPHOSPHATE TRANSPORT REGULATOR; ANKH
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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">*605145</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</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="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/605145">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<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 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=ENSG00000154122;t=ENST00000284268" 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=56172" 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=605145" 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 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 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=ENSG00000154122;t=ENST00000284268" 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_054027,XM_011514067,XM_017009644" 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_054027" 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=605145" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=05509&isoform_id=05509_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/ANKH" 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/9502217,14602635,15778896,16905507,17366849,37182129,62896821,119628439,119628440,189054654,193786000,767934496,929654582,1034645469,2462603240" 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/Q9HCJ1" 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=56172" 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=ENSG00000154122;t=ENST00000284268" 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=ANKH" 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=ANKH" 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+56172" 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/ANKH" 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:56172" 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/56172" 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=chr5&hgg_gene=ENST00000284268.8&hgg_start=14704800&hgg_end=14871778&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:15492" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/ankh" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=605145[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=605145[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/ANKH/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/ENSG00000154122" 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=ANKH" 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=ANKH" 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=ANKH" 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=ANKH&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/PA24801" 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:15492" 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://www.mousephenotype.org/data/genes/MGI:3045421" 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/ANKH#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:3045421" 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/56172/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=56172" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-2458" 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=ANKH&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
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605145
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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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ANKH INORGANIC PYROPHOSPHATE TRANSPORT REGULATOR; ANKH
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
ANK, MOUSE, HOMOLOG OF<br />
|
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HANK
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ANKH" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ANKH</a></em></strong>
|
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/5/60?start=-3&limit=10&highlight=60">5p15.2</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:14704800-14871778&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'})">5:14,704,800-14,871,778</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
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<a href="/clinicalSynopsis/table?mimNumber=118600,123000" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
|
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</span>
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</th>
|
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<th>
|
|
Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
|
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</th>
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<th>
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Phenotype <br /> mapping key
|
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</th>
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</tr>
|
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</thead>
|
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<tbody>
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<tr>
|
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<td rowspan="2">
|
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<span class="mim-font">
|
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<a href="/geneMap/5/60?start=-3&limit=10&highlight=60">
|
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5p15.2
|
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</a>
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Chondrocalcinosis 2
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</span>
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/118600"> 118600 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Craniometaphyseal dysplasia
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/123000"> 123000 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/605145" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/605145" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
|
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<br />
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</div>
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<div>
|
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<a id="text" class="mim-anchor"></a>
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<h4>
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<p>ANKH is a highly conserved transmembrane pyrophosphate transporter that channels intracellular pyrophosphate into extracellular matrix, where it acts as a potent inhibitor of mineralization (<a href="#3" class="mim-tip-reference" title="Chen, I.-P., Wang, L., Jiang, X., Aguila, H. L., Reichenberger, E. J. <strong>A Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD).</strong> Hum. Molec. Genet. 20: 948-961, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21149338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21149338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21149338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddq541" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21149338">Chen et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21149338" 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>Mutation at the mouse 'progressive ankylosis' (ank) locus causes a generalized, progressive form of arthritis accompanied by mineral deposition, formation of bony outgrowths, and joint destruction. <a href="#6" class="mim-tip-reference" title="Ho, A. M., Johnson, M. D., Kingsley, D. M. <strong>Role of the mouse ank gene in control of tissue calcification and arthritis.</strong> Science 289: 265-270, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10894769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10894769</a>] [<a href="https://doi.org/10.1126/science.289.5477.265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10894769">Ho et al. (2000)</a> showed that the ank locus encodes a multipass transmembrane protein that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. Using a positional cloning approach, <a href="#6" class="mim-tip-reference" title="Ho, A. M., Johnson, M. D., Kingsley, D. M. <strong>Role of the mouse ank gene in control of tissue calcification and arthritis.</strong> Science 289: 265-270, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10894769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10894769</a>] [<a href="https://doi.org/10.1126/science.289.5477.265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10894769">Ho et al. (2000)</a> identified the mouse Ank gene. Using the exon/intron structure of the mouse gene and partial sequence from human EST clones, <a href="#6" class="mim-tip-reference" title="Ho, A. M., Johnson, M. D., Kingsley, D. M. <strong>Role of the mouse ank gene in control of tissue calcification and arthritis.</strong> Science 289: 265-270, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10894769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10894769</a>] [<a href="https://doi.org/10.1126/science.289.5477.265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10894769">Ho et al. (2000)</a> amplified and sequenced the complete coding region of human ANK. Orthologs of mouse Ank were also found in zebrafish, rat, and cow. The human ANK gene is virtually identical to mouse ank, with only 9 amino acid differences over a 492-amino acid protein. There are 3 potential N-linked glycosylation sites and multiple putative phosphorylation sites. A hydropathy analysis revealed 9 to 12 hydrophobic stretches, most approximately 20 residues long, as would be expected for membrane-spanning regions in an integral multipass transmembrane protein. Western blot analysis suggested that the ank protein is expressed at the cell surface. Northern blot analysis revealed that ank mRNA is expressed in many tissues in adult mice, including heart, brain, liver, spleen, lung, muscle, and kidney. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10894769" 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>Although soft tissue phenotypes had not been reported in ank mice, <a href="#6" class="mim-tip-reference" title="Ho, A. M., Johnson, M. D., Kingsley, D. M. <strong>Role of the mouse ank gene in control of tissue calcification and arthritis.</strong> Science 289: 265-270, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10894769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10894769</a>] [<a href="https://doi.org/10.1126/science.289.5477.265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10894769">Ho et al. (2000)</a> observed increased calcification in kidneys of adult mice, consistent with an important role for the gene in nonskeletal tissues. Fibroblasts from ank mutants displayed about a 2-fold increase in intracellular inorganic pyrophosphate levels over wildtype cells and there was a 3- to 5-fold decrease in extracellular pyrophosphate levels. Additional studies demonstrated that ANK functions through a probenecid-sensitive anion transport mechanism. <a href="#6" class="mim-tip-reference" title="Ho, A. M., Johnson, M. D., Kingsley, D. M. <strong>Role of the mouse ank gene in control of tissue calcification and arthritis.</strong> Science 289: 265-270, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10894769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10894769</a>] [<a href="https://doi.org/10.1126/science.289.5477.265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10894769">Ho et al. (2000)</a> suggested that these results identified ANK-mediated control of pyrophosphate levels as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10894769" 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 radiation hybrid mapping, <a href="#6" class="mim-tip-reference" title="Ho, A. M., Johnson, M. D., Kingsley, D. M. <strong>Role of the mouse ank gene in control of tissue calcification and arthritis.</strong> Science 289: 265-270, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10894769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10894769</a>] [<a href="https://doi.org/10.1126/science.289.5477.265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10894769">Ho et al. (2000)</a> mapped the human ANK gene to chromosome 5p, in a region showing homology of synteny with proximal mouse chromosome 15. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10894769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Nurnberg, P., Thiele, H., Chandler, D., Hohne, W., Cunningham, M. L., Ritter, H., Leschik, G., Uhlmann, K., Mischung, C., Harrop, K., Goldblatt, J., Borochowitz, Z. U., Kotzot, D., Westermann, F., Mundlos, S., Braun, H.-S., Laing, N., Tinschert, S. <strong>Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.</strong> Nature Genet. 28: 37-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326272</a>] [<a href="https://doi.org/10.1038/ng0501-37" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326272">Nurnberg et al. (2001)</a> stated that the ANKH gene maps to chromosome 5p15.2-p14.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11326272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 3/26/2014."None>Gross (2014)</a> mapped the ANKH gene to chromosome 5p15.2 based on an alignment of the ANKH sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF274753" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF274753</a>) with the genomic sequence (GRCh37).</p>
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<p><strong><em>Craniometaphyseal Dysplasia</em></strong></p><p>
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Craniometaphyseal dysplasia is a bone dysplasia characterized by overgrowth and sclerosis of the craniofacial bones and abnormal modeling of the metaphyses of the tubular bones. Hyperostosis and sclerosis of the skull may lead to cranial nerve compressions resulting in hearing loss and facial palsy. An autosomal dominant form of the disorder (CMDD; <a href="/entry/123000">123000</a>) was mapped to 5p15.2-p14.1 (<a href="#10" class="mim-tip-reference" title="Nurnberg, P., Tinschert, S., Mrug, M., Hampe, J., Muller, C. R., Fuhrmann, E., Braun, H.-S., Reis, A. <strong>The gene for autosomal dominant craniometaphyseal dysplasia maps to chromosome 5q and is distinct from the growth hormone-receptor gene.</strong> Am. J. Hum. Genet. 61: 918-923, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9382103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9382103</a>] [<a href="https://doi.org/10.1086/514880" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9382103">Nurnberg et al., 1997</a>) within a region harboring the human homolog (ANKH) of the mouse progressive ankylosis (ank) gene. The ANK protein spans the outer cell membrane and shuttles inorganic pyrophosphate, a major inhibitor of physiologic and pathologic calcification, bone mineralization, and bone resorption. <a href="#9" class="mim-tip-reference" title="Nurnberg, P., Thiele, H., Chandler, D., Hohne, W., Cunningham, M. L., Ritter, H., Leschik, G., Uhlmann, K., Mischung, C., Harrop, K., Goldblatt, J., Borochowitz, Z. U., Kotzot, D., Westermann, F., Mundlos, S., Braun, H.-S., Laing, N., Tinschert, S. <strong>Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.</strong> Nature Genet. 28: 37-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326272</a>] [<a href="https://doi.org/10.1038/ng0501-37" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326272">Nurnberg et al. (2001)</a> identified 6 different heterozygous mutations in the ANKH gene in 8 of 9 families with CMDD (see, e.g., <a href="#0001">605145.0001</a>-<a href="#0005">605145.0005</a>). The mutations predicted single amino acid substitutions, deletions, or insertions. Using a helix prediction program, they proposed for the ANK molecule 12 membrane-spanning helices with an alternate inside/out orientation and a central channel permitting the passage of inorganic pyrophosphate. The mutations occurred at highly conserved amino acid residues presumed to be located in the cytosolic portion of the protein. The results linked the inorganic pyrophosphate channel ANK with bone formation and remodeling. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9382103+11326272" 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="Reichenberger, E., Tiziani, V., Watanabe, S., Park, L., Ueki, Y., Santanna, C., Baur, S. T., Shiang, R., Grange, D. K., Beighton, P., Gardner, J., Hamersma, H., Sellars, S., Ramesar, R., Lidral, A. C., Sommer, A., Raposo do Amaral, C. M., Gorlin, R. J., Mulliken, J. B., Olsen, B. R. <strong>Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK.</strong> Am. J. Hum. Genet. 68: 1321-1326, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11326338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/320612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326338">Reichenberger et al. (2001)</a> demonstrated 3 different mutations in the ANKH gene in 5 different families and in isolated cases of CMDD. All mutations clustered within 7 amino acids in 1 of the 6 possible cytosolic domains of the ANKH protein. These results suggested that the mutated protein has a dominant-negative effect on its function, since reduced levels of pyrophosphate in bone matrix increase mineralization. Progressive thickening and increased mineral density of craniofacial bones and abnormally developed metaphyses in the long bones characterize CMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11326338" 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>Chondrocalcinosis-2</em></strong></p><p>
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Chondrocalcinosis is a common cause of joint pain and arthritis that is caused by the deposition of calcium-containing crystals within articular cartilage. <a href="#11" class="mim-tip-reference" title="Pendleton, A., Johnson, M. D., Hughes, A., Gurley, K. A., Ho, A. M., Doherty, M., Dixey, J., Gillet, P., Loeuille, D., McGrath, R., Reginato, A., Shiang, R., Wright, G., Netter, P., Williams, C., Kingsley, D. M. <strong>Mutations in ANKH cause chondrocalcinosis.</strong> Am. J. Hum. Genet. 71: 933-940, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12297987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12297987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12297987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/343054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12297987">Pendleton et al. (2002)</a> showed that affected members of 2 previously described families with chondrocalcinosis-2 (CCAL2; <a href="/entry/118600">118600</a>), which is also called calcium pyrophosphate dihydrate deposition disease (CPPDD), had mutations in the ANKH gene. One of the mutations resulted in the substitution of a highly conserved amino acid residue within a predicted transmembrane segment (<a href="#0006">605145.0006</a>); the other created a new ATG start site that added 4 additional residues to the ANKH protein (<a href="#0007">605145.0007</a>). In addition, 1 of 95 patients with sporadic chondrocalcinosis from the U.K. showed a deletion of a single codon in the ANKH gene (<a href="#0008">605145.0008</a>). The same change was found in the patient's sister and son; the sister had bilateral knee replacement for osteoarthritis. Each of the 3 mutations was reconstructed in a full-length ANK expression construct previously shown to regulate pyrophosphate levels in cultured cells in vitro. All 3 mutations showed significantly more activity than a previously described nonsense mutation that causes severe hydroxyapatite mineral deposition and widespread joint ankylosis in mice. These results suggested that small sequence changes in ANKH are 1 cause of chondrocalcinosis and joint disease in humans. Increased ANK activity may explain the different types of crystals commonly deposited in CCAL2 families and mutant mice, and may provide a useful pharmacologic target for treating some forms of human chondrocalcinosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12297987" 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 family with calcium pyrophosphate dihydrate deposition disease, <a href="#17" class="mim-tip-reference" title="Williams, C. J., Zhang, Y., Timms, A., Bonavita, G., Caeiro, F., Broxholme, J., Cuthbertson, J., Jones, Y., Marchegiani, R., Reginato, A., Russell, R. G. G., Wordsworth, B. P., Carr, A. J., Brown, M. A. <strong>Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH.</strong> Am. J. Hum. Genet. 71: 985-991, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12297989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12297989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12297989[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/343053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12297989">Williams et al. (2002)</a> identified a pro5-to-leu (<a href="#0009">605145.0009</a>) mutation in the ANKH gene. They postulated that loss of function of ANKH causes elevated extracellular inorganic pyrophosphate levels, predisposing to CCAL2 crystal deposition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12297989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Williams, C. J., Pendleton, A., Bonavita, G., Reginato, A. J., Hughes, A. E., Peariso, S., Doherty, M., McCarty, D. J., Ryan, L. M. <strong>Mutations in the amino terminus of ANKH in two US families with calcium pyrophosphate dihydrate crystal deposition disease.</strong> Arthritis Rheum. 48: 2627-2631, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13130483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13130483</a>] [<a href="https://doi.org/10.1002/art.11133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13130483">Williams et al. (2003)</a> screened for mutations in the ANKH gene in 2 U.S. families with autosomal dominant CPPDD and found that all affected members were heterozygous for a pro5-to-thr mutation (<a href="#0010">605145.0010</a>). The 2 families displayed distinct haplotypes. <a href="#16" class="mim-tip-reference" title="Williams, C. J., Pendleton, A., Bonavita, G., Reginato, A. J., Hughes, A. E., Peariso, S., Doherty, M., McCarty, D. J., Ryan, L. M. <strong>Mutations in the amino terminus of ANKH in two US families with calcium pyrophosphate dihydrate crystal deposition disease.</strong> Arthritis Rheum. 48: 2627-2631, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13130483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13130483</a>] [<a href="https://doi.org/10.1002/art.11133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13130483">Williams et al. (2003)</a> noted that the family described by <a href="#17" class="mim-tip-reference" title="Williams, C. J., Zhang, Y., Timms, A., Bonavita, G., Caeiro, F., Broxholme, J., Cuthbertson, J., Jones, Y., Marchegiani, R., Reginato, A., Russell, R. G. G., Wordsworth, B. P., Carr, A. J., Brown, M. A. <strong>Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH.</strong> Am. J. Hum. Genet. 71: 985-991, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12297989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12297989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12297989[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/343053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12297989">Williams et al. (2002)</a> had a different mutation at the same codon (see <a href="#0009">605145.0009</a>) and also displayed a distinct haplotype. They concluded that the evolutionarily conserved pro5 position of ANKH may represent a hotspot for mutation in families with autosomal dominant CCAL2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13130483+12297989" 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>Mutations in the progressive ankylosis gene (Ank/ANKH) cause surprisingly different skeletal phenotypes in mice and humans. Ank encodes a multiple-pass transmembrane protein that regulates pyrophosphate levels inside and outside tissue culture cells; conflicting models have been proposed to explain the effects of the human mutations. <a href="#5" class="mim-tip-reference" title="Gurley, K. A., Reimer, R. J., Kingsley, D. M. <strong>Biochemical and genetic analysis of ANK in arthritis and bone disease.</strong> Am. J. Hum. Genet. 79: 1017-1029, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17186460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17186460</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17186460[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/509881" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17186460">Gurley et al. (2006)</a> tested wildtype and mutant forms of ANK for radiolabeled pyrophosphate-transport activity in frog oocytes. They also reconstructed 2 human mutations in a bacterial artificial chromosome and tested them in transgenic mice for rescue of the Ank-null phenotype and for induction of new skeletal phenotypes. Wildtype ANK stimulates saturable transport of pyrophosphate ions across the plasma membrane, with half maximal rates attained at physiologic levels of pyrophosphate. Chondrocalcinosis mutations retain apparently wildtype transport activity and can rescue the joint-fusion phenotype of Ank-null mice. Craniometaphyseal dysplasia mutations do not transport pyrophosphate and cannot rescue the defects of Ank-null mice. Furthermore, microcomputed tomography revealed previously unappreciated phenotypes in Ank-null mice that are reminiscent of craniometaphyseal dysplasia. The combination of biochemical and genetic analyses provided insight into how mutations in ANKH cause human skeletal disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17186460" 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 an Australian family with CMDD and a known mutation in the ANKH gene (G389R; <a href="#0002">605145.0002</a>), <a href="#2" class="mim-tip-reference" title="Baynam, G., Goldblatt, J., Schofield, L. <strong>Craniometaphyseal dysplasia and chondrocalcinosis cosegregating in a family with an ANKH mutation. (Letter)</strong> Am. J. Med. Genet. 149A: 1331-1333, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19449425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19449425</a>] [<a href="https://doi.org/10.1002/ajmg.a.32875" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19449425">Baynam et al. (2009)</a> found evidence for chondrocalcinosis segregating with CMDD in mutation-positive female family members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19449425" 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>Mice carrying the progressive ankylosis mutation have been studied as a model of arthritis. The autosomal recessive Ank mutation causes an abnormal flat-footed gait in young mice due to decreased mobility of ankle and toe joints. Loss of joint mobility becomes more severe with age and spreads to most joints throughout the limbs and vertebral column leading to complete rigidity and death around 6 months of age. Hydroxyapatite crystals develop in articular surfaces and synovial fluid of Ank mice, accompanied by joint space narrowing, cartilage erosion, and formation of bony outgrowths or osteophytes that cause fusion (ankylosis) and joint immobility. <a href="#6" class="mim-tip-reference" title="Ho, A. M., Johnson, M. D., Kingsley, D. M. <strong>Role of the mouse ank gene in control of tissue calcification and arthritis.</strong> Science 289: 265-270, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10894769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10894769</a>] [<a href="https://doi.org/10.1126/science.289.5477.265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10894769">Ho et al. (2000)</a> identified a G-to-T substitution in the mouse Ank gene, leading to a nonsense mutation in exon 11, the penultimate exon of mouse Ank. This mutation truncates the C-terminal region of the protein and greatly reduces its activity in vitro. The mouse Ank gene is expressed in developing articular surfaces and may help maintain the unmineralized state by providing a local source of inorganic pyrophosphate to inhibit hydroxyapatite formation. In the absence of normal Ank activity, mineralization extends unhindered throughout articular cartilage, hydroxyapatite deposits form in synovial fluid, and new bone is deposited in and around joints, showing that the gene is essential for normal joint maintenance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10894769" 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="#3" class="mim-tip-reference" title="Chen, I.-P., Wang, L., Jiang, X., Aguila, H. L., Reichenberger, E. J. <strong>A Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD).</strong> Hum. Molec. Genet. 20: 948-961, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21149338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21149338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21149338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddq541" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21149338">Chen et al. (2011)</a> created knockin (KI) mice overexpressing human ANK with the phe377 deletion (<a href="#0001">605145.0001</a>) associated with craniometaphyseal dysplasia. Ank KI/KI mice exhibited increased bone mass in craniofacial bones, especially in mandibles, excessive trabecular bone in diaphyses of long bones, and hypomineralization of cortex of long bones. Metaphyses were undertrabeculated. Cultured Ank KI/KI calvarial osteoblasts and bone marrow stromal cells showed reduced mineral nodule formation compared with wildtype controls. Mature osteoclasts derived from Ank KI/KI bone marrow progenitors were reduced in size, showed a disrupted actin ring, produced fewer multinucleated osteoclasts, and displayed reduced cell migration. Extracellular pyrophosphate was normal in Ank KI/KI osteoblasts, apparently due to compensatory upregulation of Pc1 (ENPP1; <a href="/entry/173335">173335</a>), another regulator of extracellular pyrophosphate. <a href="#3" class="mim-tip-reference" title="Chen, I.-P., Wang, L., Jiang, X., Aguila, H. L., Reichenberger, E. J. <strong>A Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD).</strong> Hum. Molec. Genet. 20: 948-961, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21149338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21149338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21149338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddq541" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21149338">Chen et al. (2011)</a> found that peripheral blood mononuclear cells of adult craniometaphyseal dysplasia patients also showed defective osteoclastogenesis, with reduced number of multinucleated osteoclasts and reduced mineral resorption. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21149338" 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=605145[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>In 2 apparently unrelated German families with craniometaphyseal dysplasia (<a href="/entry/123000">123000</a>), previously reported by <a href="#14" class="mim-tip-reference" title="Spranger, J. W., Paulsen, K., Lehmann, W. <strong>Die kraniometaphysaere Dysplasie (Pyle).</strong> Z. Kinderheilk. 93: 64-79, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14322785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14322785</a>]" pmid="14322785">Spranger et al. (1965)</a> and <a href="#13" class="mim-tip-reference" title="Schwahn, B., Schaper, J., Herkenrath, P., Michel, O., Schonau, E. <strong>Chronic recurrent multifocal osteomyelitis with MR correlation: a case report.</strong> Monatsschr. Kinderheilkd. 144: 1073-1077, 1996."None>Schwahn et al. (1996)</a>, <a href="#9" class="mim-tip-reference" title="Nurnberg, P., Thiele, H., Chandler, D., Hohne, W., Cunningham, M. L., Ritter, H., Leschik, G., Uhlmann, K., Mischung, C., Harrop, K., Goldblatt, J., Borochowitz, Z. U., Kotzot, D., Westermann, F., Mundlos, S., Braun, H.-S., Laing, N., Tinschert, S. <strong>Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.</strong> Nature Genet. 28: 37-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326272</a>] [<a href="https://doi.org/10.1038/ng0501-37" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326272">Nurnberg et al. (2001)</a> found deletion of 3 basepairs leading to deletion of codon 377 (phenylalanine). Because of different haplotype backgrounds, these were thought to be recurrent mutations, an interpretation favored by a short tandem repeat structure for F377del (1196delCTT). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14322785+11326272" 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="Reichenberger, E., Tiziani, V., Watanabe, S., Park, L., Ueki, Y., Santanna, C., Baur, S. T., Shiang, R., Grange, D. K., Beighton, P., Gardner, J., Hamersma, H., Sellars, S., Ramesar, R., Lidral, A. C., Sommer, A., Raposo do Amaral, C. M., Gorlin, R. J., Mulliken, J. B., Olsen, B. R. <strong>Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK.</strong> Am. J. Hum. Genet. 68: 1321-1326, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11326338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/320612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326338">Reichenberger et al. (2001)</a> reported the same mutation in affected members of 2 families with craniometaphyseal dysplasia. They designated the mutation PHE376DEL (1127delTCT) based on a different numbering system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11326338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28939080 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939080;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28939080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28939080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005502 OR RCV000032998" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005502, RCV000032998" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005502...</a>
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<p>In a Swiss family and an Australian family with craniometaphyseal dysplasia (CMDD; <a href="/entry/123000">123000</a>), the latter family originally reported by <a href="#15" class="mim-tip-reference" title="Taylor, D. B., Sprague, P. <strong>Dominant craniometaphyseal dysplasia: a family study over five generations.</strong> Australas. Radiol. 33: 84-89, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2712793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2712793</a>] [<a href="https://doi.org/10.1111/j.1440-1673.1989.tb03242.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2712793">Taylor and Sprague (1989)</a>, <a href="#9" class="mim-tip-reference" title="Nurnberg, P., Thiele, H., Chandler, D., Hohne, W., Cunningham, M. L., Ritter, H., Leschik, G., Uhlmann, K., Mischung, C., Harrop, K., Goldblatt, J., Borochowitz, Z. U., Kotzot, D., Westermann, F., Mundlos, S., Braun, H.-S., Laing, N., Tinschert, S. <strong>Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.</strong> Nature Genet. 28: 37-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326272</a>] [<a href="https://doi.org/10.1038/ng0501-37" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326272">Nurnberg et al. (2001)</a> identified a gly389-to-arg (G389R) missense mutation in the ANKH gene as the basis of craniometaphyseal dysplasia. That these were recurrent mutations was supported by the fact that they were on different haplotype backgrounds and by the nature of the affected sequence, namely, a CpG dinucleotide for G389R (1233G-A). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11326272+2712793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Baynam, G., Goldblatt, J., Schofield, L. <strong>Craniometaphyseal dysplasia and chondrocalcinosis cosegregating in a family with an ANKH mutation. (Letter)</strong> Am. J. Med. Genet. 149A: 1331-1333, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19449425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19449425</a>] [<a href="https://doi.org/10.1002/ajmg.a.32875" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19449425">Baynam et al. (2009)</a> restudied the Australian family with CMDD that was originally reported by <a href="#15" class="mim-tip-reference" title="Taylor, D. B., Sprague, P. <strong>Dominant craniometaphyseal dysplasia: a family study over five generations.</strong> Australas. Radiol. 33: 84-89, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2712793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2712793</a>] [<a href="https://doi.org/10.1111/j.1440-1673.1989.tb03242.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2712793">Taylor and Sprague (1989)</a> and found evidence for chondrocalcinosis segregating with CMDD in mutation-positive female family members. Although a chance association of chondrocalcinosis with CMDD could not be excluded, <a href="#2" class="mim-tip-reference" title="Baynam, G., Goldblatt, J., Schofield, L. <strong>Craniometaphyseal dysplasia and chondrocalcinosis cosegregating in a family with an ANKH mutation. (Letter)</strong> Am. J. Med. Genet. 149A: 1331-1333, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19449425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19449425</a>] [<a href="https://doi.org/10.1002/ajmg.a.32875" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19449425">Baynam et al. (2009)</a> suggested that the lack of joint symptoms in affected male family members might be due to involvement of sex-dependent mechanisms or to the fact that only mutation-positive women in the pedigree had reached the age at which the chondrocalcinosis phenotype typically expresses. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19449425+2712793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1579998709 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1579998709;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1579998709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1579998709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005503 OR RCV001851668" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005503, RCV001851668" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005503...</a>
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<p>In a patient with craniometaphyseal dysplasia (<a href="/entry/123000">123000</a>), <a href="#9" class="mim-tip-reference" title="Nurnberg, P., Thiele, H., Chandler, D., Hohne, W., Cunningham, M. L., Ritter, H., Leschik, G., Uhlmann, K., Mischung, C., Harrop, K., Goldblatt, J., Borochowitz, Z. U., Kotzot, D., Westermann, F., Mundlos, S., Braun, H.-S., Laing, N., Tinschert, S. <strong>Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.</strong> Nature Genet. 28: 37-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326272</a>] [<a href="https://doi.org/10.1038/ng0501-37" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326272">Nurnberg et al. (2001)</a> identified an insertion of a single alanine in the ANKH cDNA; the mutation, however, was an A-to-G transition in the splice acceptor site of intron 9 that ended with a split codon, which contributed to the codon (GCA) for the extra alanine. A new splice acceptor site in the disease allele was created by the heterozygous point mutation at position -4 of the splice donor site of intron 9. <a href="#12" class="mim-tip-reference" title="Reichenberger, E., Tiziani, V., Watanabe, S., Park, L., Ueki, Y., Santanna, C., Baur, S. T., Shiang, R., Grange, D. K., Beighton, P., Gardner, J., Hamersma, H., Sellars, S., Ramesar, R., Lidral, A. C., Sommer, A., Raposo do Amaral, C. M., Gorlin, R. J., Mulliken, J. B., Olsen, B. R. <strong>Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK.</strong> Am. J. Hum. Genet. 68: 1321-1326, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11326338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/320612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326338">Reichenberger et al. (2001)</a> identified the same mutation in affected members of a family with craniometaphyseal dysplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11326338+11326272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908406 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908406;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005504 OR RCV001090992" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005504, RCV001090992" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005504...</a>
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<p>In 2 affected members of a family with craniometaphyseal dysplasia (<a href="/entry/123000">123000</a>), <a href="#9" class="mim-tip-reference" title="Nurnberg, P., Thiele, H., Chandler, D., Hohne, W., Cunningham, M. L., Ritter, H., Leschik, G., Uhlmann, K., Mischung, C., Harrop, K., Goldblatt, J., Borochowitz, Z. U., Kotzot, D., Westermann, F., Mundlos, S., Braun, H.-S., Laing, N., Tinschert, S. <strong>Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.</strong> Nature Genet. 28: 37-41, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326272</a>] [<a href="https://doi.org/10.1038/ng0501-37" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326272">Nurnberg et al. (2001)</a> identified a 3-bp deletion (1192delCTT) in exon 9 of the ANKH gene, resulting in the deletion of ser375. In 2 sporadic cases of craniometaphyseal dysplasia, <a href="#12" class="mim-tip-reference" title="Reichenberger, E., Tiziani, V., Watanabe, S., Park, L., Ueki, Y., Santanna, C., Baur, S. T., Shiang, R., Grange, D. K., Beighton, P., Gardner, J., Hamersma, H., Sellars, S., Ramesar, R., Lidral, A. C., Sommer, A., Raposo do Amaral, C. M., Gorlin, R. J., Mulliken, J. B., Olsen, B. R. <strong>Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK.</strong> Am. J. Hum. Genet. 68: 1321-1326, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11326338[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/320612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326338">Reichenberger et al. (2001)</a> found the same 3-bp deletion, which they designated 1122delCTC based on a different numbering system. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11326338+11326272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908407 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908407;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908407" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908407" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005505" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005505" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005505</a>
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<p>In a French family with chondrocalcinosis-2 (<a href="/entry/118600">118600</a>) reported by <a href="#1" class="mim-tip-reference" title="Andrew, L. J., Brancolini, V., Serrano de la Pena, L., Devoto, M., Caeiro, F., Marchegiani, R., Reginato, A., Gaucher, A., Netter, P., Gillet, P., Loeuille, D., Prockop, D. J., Carr, A., Wordsworth, B. F., Lathrop, M., Butcher, S., Considine, E., Everts, K., Nicod, A., Walsh, S., Williams, C. J. <strong>Refinement of the chromosome 5p locus for familial calcium pyrophosphate dihydrate deposition disease.</strong> Am. J. Hum. Genet. 64: 136-145, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9915952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9915952</a>] [<a href="https://doi.org/10.1086/302186" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9915952">Andrew et al. (1999)</a>, <a href="#11" class="mim-tip-reference" title="Pendleton, A., Johnson, M. D., Hughes, A., Gurley, K. A., Ho, A. M., Doherty, M., Dixey, J., Gillet, P., Loeuille, D., McGrath, R., Reginato, A., Shiang, R., Wright, G., Netter, P., Williams, C., Kingsley, D. M. <strong>Mutations in ANKH cause chondrocalcinosis.</strong> Am. J. Hum. Genet. 71: 933-940, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12297987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12297987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12297987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/343054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12297987">Pendleton et al. (2002)</a> found that affected members were heterozygous for a 143T-C transition in exon 2 of the ANKH gene, resulting in a met48-to-thr (M48T) substitution. The mutation is in a transmembrane domain at a position that is absolutely conserved in the ANKH protein over 400 million years of evolution from fish to mammals. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9915952+12297987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2126640512 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2126640512;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2126640512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2126640512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005506" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005506" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005506</a>
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<p>In a British family with chondrocalcinosis-2 (<a href="/entry/118600">118600</a>) reported by <a href="#7" class="mim-tip-reference" title="Hughes, A. E., McGibbon, D., Woodward, E., Dixey, J., Doherty, M. <strong>Localisation of a gene for chondrocalcinosis to chromosome 5p.</strong> Hum. Molec. Genet. 4: 1225-1228, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528213</a>] [<a href="https://doi.org/10.1093/hmg/4.7.1225" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528213">Hughes et al. (1995)</a>, <a href="#11" class="mim-tip-reference" title="Pendleton, A., Johnson, M. D., Hughes, A., Gurley, K. A., Ho, A. M., Doherty, M., Dixey, J., Gillet, P., Loeuille, D., McGrath, R., Reginato, A., Shiang, R., Wright, G., Netter, P., Williams, C., Kingsley, D. M. <strong>Mutations in ANKH cause chondrocalcinosis.</strong> Am. J. Hum. Genet. 71: 933-940, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12297987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12297987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12297987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/343054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12297987">Pendleton et al. (2002)</a> found that affected members were heterozygous for a -11C-T change located 11-bp upstream of the normal ATG initiation codon of the ANKH gene. This change generated an alternative ATG initiation codon and added 4 amino acids to the highly conserved N terminus of the ANKH protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8528213+12297987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 CHONDROCALCINOSIS 2, SPORADIC</strong>
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ANKH, GLU490DEL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121908408 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908408;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121908408?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908408" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908408" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005507" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005507" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005507</a>
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<p>In 1 of 95 British patients with sporadic chondrocalcinosis-2 (<a href="/entry/118600">118600</a>), <a href="#11" class="mim-tip-reference" title="Pendleton, A., Johnson, M. D., Hughes, A., Gurley, K. A., Ho, A. M., Doherty, M., Dixey, J., Gillet, P., Loeuille, D., McGrath, R., Reginato, A., Shiang, R., Wright, G., Netter, P., Williams, C., Kingsley, D. M. <strong>Mutations in ANKH cause chondrocalcinosis.</strong> Am. J. Hum. Genet. 71: 933-940, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12297987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12297987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12297987[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/343054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12297987">Pendleton et al. (2002)</a> identified a 3-bp deletion in exon 12 of the ANKH gene that deleted a glutamate residue (E490del) located 3 amino acids from the highly conserved C terminus of the ANKH protein. The 79-year-old proband had a sister who had undergone bilateral knee replacements for 'osteoarthritis.' The sister and son of the proband were heterozygous for this ANKH mutation, but the son was not yet old enough for a reliable diagnosis of chondrocalcinosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12297987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<strong>.0009 CHONDROCALCINOSIS 2</strong>
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ANKH, PRO5LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908409 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908409;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005508 OR RCV004719627" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005508, RCV004719627" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005508...</a>
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<p>In a family with autosomal dominant familial calcium pyrophosphate dihydrate deposition disease (<a href="/entry/118600">118600</a>), <a href="#17" class="mim-tip-reference" title="Williams, C. J., Zhang, Y., Timms, A., Bonavita, G., Caeiro, F., Broxholme, J., Cuthbertson, J., Jones, Y., Marchegiani, R., Reginato, A., Russell, R. G. G., Wordsworth, B. P., Carr, A. J., Brown, M. A. <strong>Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH.</strong> Am. J. Hum. Genet. 71: 985-991, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12297989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12297989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12297989[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/343053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12297989">Williams et al. (2002)</a> identified a C-to-T transition at 14 bp from the start codon of the ANKH gene, resulting in a pro5-to-leu (P5L) change, which segregated with the disease. Some members of the family with the disease haplotype were considered too young to manifest the disorder; some other members of the family did not have the disease haplotype but were apparently affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12297989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 CHONDROCALCINOSIS 2</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908410 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908410;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005509 OR RCV004734498" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005509, RCV004734498" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005509...</a>
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<p><a href="#16" class="mim-tip-reference" title="Williams, C. J., Pendleton, A., Bonavita, G., Reginato, A. J., Hughes, A. E., Peariso, S., Doherty, M., McCarty, D. J., Ryan, L. M. <strong>Mutations in the amino terminus of ANKH in two US families with calcium pyrophosphate dihydrate crystal deposition disease.</strong> Arthritis Rheum. 48: 2627-2631, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13130483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13130483</a>] [<a href="https://doi.org/10.1002/art.11133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13130483">Williams et al. (2003)</a> screened 2 US families with autosomal dominant calcium pyrophosphate dihydrate deposition disease (<a href="/entry/118600">118600</a>) for mutations in the ANKH gene and found that all affected members were heterozygous for a pro5-to-thr (P5T) mutation. They noted that another mutation at the same codon (P5L; <a href="#0009">605145.0009</a>) had previously been reported to cause the same disorder and suggested that the evolutionarily conserved P5 position of ANKH may represent a hotspot for mutation in families with autosomal dominant CPPDD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13130483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606656 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606656;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267606656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267606656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005510" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005510" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005510</a>
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<p>In a French boy with craniometaphyseal dysplasia (<a href="/entry/123000">123000</a>), <a href="#8" class="mim-tip-reference" title="Kornak, U., Brancati, F., Le Merrer, M., Lichtenbelt, K., Hohne, W., Tinschert, S., Garaci, F. G., Dallapiccola, B., Nurnberg, P. <strong>Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss.</strong> Am. J. Med. Genet. 152A: 870-874, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20358596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20358596</a>] [<a href="https://doi.org/10.1002/ajmg.a.33301" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20358596">Kornak et al. (2010)</a> identified a heterozygous 1015T-C transition in exon 9 of the ANKH gene, resulting in a cys339-to-arg (C339R) substitution in a highly conserved residue in transmembrane helix 9. The patient had a severe form of the disorder, with hearing loss and bilateral facial palsy developing soon after birth. He had severe sclerosis of the skull base, orbits, maxilla, and mandible, with almost complete obstruction of the sinuses. There was rapid worsening of the bone phenotype in the first years of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20358596" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
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ANKH, LEU391PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606658 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606658;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267606658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267606658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005511" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005511" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005511</a>
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<p>In a 24-year-old man from the Netherlands with craniometaphyseal dysplasia (<a href="/entry/123000">123000</a>), <a href="#8" class="mim-tip-reference" title="Kornak, U., Brancati, F., Le Merrer, M., Lichtenbelt, K., Hohne, W., Tinschert, S., Garaci, F. G., Dallapiccola, B., Nurnberg, P. <strong>Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss.</strong> Am. J. Med. Genet. 152A: 870-874, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20358596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20358596</a>] [<a href="https://doi.org/10.1002/ajmg.a.33301" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20358596">Kornak et al. (2010)</a> identified a heterozygous 1172T-C transition in exon 10 of the ANKH gene, resulting in a leu391-to-pro (L391P) substitution in a highly conserved residue in the loop between transmembrane helices 10 and 11. The patient presented with progressive conductive and sensorineural hearing loss and was found to have typical features of the disorder, with unilateral facial palsy apparent in infancy, macrocephaly, and teeth crowding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20358596" 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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<span class="mim-font">
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<strong>.0013 CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
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ANKH, LEU334ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606657 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606657;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267606657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267606657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005512" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005512" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005512</a>
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<p>In a 43-year-old Italian man with craniometaphyseal dysplasia (<a href="/entry/123000">123000</a>), <a href="#8" class="mim-tip-reference" title="Kornak, U., Brancati, F., Le Merrer, M., Lichtenbelt, K., Hohne, W., Tinschert, S., Garaci, F. G., Dallapiccola, B., Nurnberg, P. <strong>Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss.</strong> Am. J. Med. Genet. 152A: 870-874, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20358596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20358596</a>] [<a href="https://doi.org/10.1002/ajmg.a.33301" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20358596">Kornak et al. (2010)</a> identified a heterozygous 1001T-G transversion in exon 8 of the ANKH gene, resulting in a leu334-to-arg (L334R) substitution in a highly conserved residue in transmembrane helix 9. The patient had typical manifestations of CMD, with sclerosis of the skull base and maxilla, hyperostotic but not sclerotic mandible, and partially obstructed sinuses without cranial nerve compression. He also had narrowing of the middle ear cavities with bilateral fixation of the body of the incus to the lateral attic, resulting in conductive deafness and tinnitus. These middle ear manifestations were similar to those observed in postinflammatory ossicular fixation secondary to acute or chronic otitis media. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20358596" 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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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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Andrew, L. J., Brancolini, V., Serrano de la Pena, L., Devoto, M., Caeiro, F., Marchegiani, R., Reginato, A., Gaucher, A., Netter, P., Gillet, P., Loeuille, D., Prockop, D. J., Carr, A., Wordsworth, B. F., Lathrop, M., Butcher, S., Considine, E., Everts, K., Nicod, A., Walsh, S., Williams, C. J.
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[<a href="https://doi.org/10.1086/302186" target="_blank">Full Text</a>]
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<a id="Baynam2009" class="mim-anchor"></a>
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Baynam, G., Goldblatt, J., Schofield, L.
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<strong>Craniometaphyseal dysplasia and chondrocalcinosis cosegregating in a family with an ANKH mutation. (Letter)</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19449425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19449425</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19449425" 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/10.1002/ajmg.a.32875" target="_blank">Full Text</a>]
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<a id="Chen2011" class="mim-anchor"></a>
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Chen, I.-P., Wang, L., Jiang, X., Aguila, H. L., Reichenberger, E. J.
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<strong>A Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD).</strong>
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Hum. Molec. Genet. 20: 948-961, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21149338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21149338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21149338[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=21149338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddq541" target="_blank">Full Text</a>]
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<a id="Gross2014" class="mim-anchor"></a>
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 3/26/2014.
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Gurley, K. A., Reimer, R. J., Kingsley, D. M.
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<strong>Biochemical and genetic analysis of ANK in arthritis and bone disease.</strong>
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Am. J. Hum. Genet. 79: 1017-1029, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17186460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17186460</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17186460[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=17186460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/509881" target="_blank">Full Text</a>]
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Ho, A. M., Johnson, M. D., Kingsley, D. M.
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<strong>Role of the mouse ank gene in control of tissue calcification and arthritis.</strong>
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Science 289: 265-270, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10894769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10894769</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10894769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.289.5477.265" target="_blank">Full Text</a>]
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<a id="Hughes1995" class="mim-anchor"></a>
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Hughes, A. E., McGibbon, D., Woodward, E., Dixey, J., Doherty, M.
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<strong>Localisation of a gene for chondrocalcinosis to chromosome 5p.</strong>
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[<a href="https://doi.org/10.1093/hmg/4.7.1225" target="_blank">Full Text</a>]
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<a id="Kornak2010" class="mim-anchor"></a>
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Kornak, U., Brancati, F., Le Merrer, M., Lichtenbelt, K., Hohne, W., Tinschert, S., Garaci, F. G., Dallapiccola, B., Nurnberg, P.
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<strong>Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss.</strong>
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Am. J. Med. Genet. 152A: 870-874, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20358596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20358596</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20358596" 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/10.1002/ajmg.a.33301" target="_blank">Full Text</a>]
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<a id="Nurnberg2001" class="mim-anchor"></a>
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Nurnberg, P., Thiele, H., Chandler, D., Hohne, W., Cunningham, M. L., Ritter, H., Leschik, G., Uhlmann, K., Mischung, C., Harrop, K., Goldblatt, J., Borochowitz, Z. U., Kotzot, D., Westermann, F., Mundlos, S., Braun, H.-S., Laing, N., Tinschert, S.
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<strong>Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.</strong>
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Nature Genet. 28: 37-41, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326272</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11326272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng0501-37" target="_blank">Full Text</a>]
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<a id="Nurnberg1997" class="mim-anchor"></a>
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Nurnberg, P., Tinschert, S., Mrug, M., Hampe, J., Muller, C. R., Fuhrmann, E., Braun, H.-S., Reis, A.
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<strong>The gene for autosomal dominant craniometaphyseal dysplasia maps to chromosome 5q and is distinct from the growth hormone-receptor gene.</strong>
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Am. J. Hum. Genet. 61: 918-923, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9382103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9382103</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9382103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/514880" target="_blank">Full Text</a>]
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<a id="Pendleton2002" class="mim-anchor"></a>
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Pendleton, A., Johnson, M. D., Hughes, A., Gurley, K. A., Ho, A. M., Doherty, M., Dixey, J., Gillet, P., Loeuille, D., McGrath, R., Reginato, A., Shiang, R., Wright, G., Netter, P., Williams, C., Kingsley, D. M.
|
|
<strong>Mutations in ANKH cause chondrocalcinosis.</strong>
|
|
Am. J. Hum. Genet. 71: 933-940, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12297987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12297987</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12297987[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=12297987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/343054" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Reichenberger2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reichenberger, E., Tiziani, V., Watanabe, S., Park, L., Ueki, Y., Santanna, C., Baur, S. T., Shiang, R., Grange, D. K., Beighton, P., Gardner, J., Hamersma, H., Sellars, S., Ramesar, R., Lidral, A. C., Sommer, A., Raposo do Amaral, C. M., Gorlin, R. J., Mulliken, J. B., Olsen, B. R.
|
|
<strong>Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK.</strong>
|
|
Am. J. Hum. Genet. 68: 1321-1326, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11326338[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=11326338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/320612" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
|
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<a id="Schwahn1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schwahn, B., Schaper, J., Herkenrath, P., Michel, O., Schonau, E.
|
|
<strong>Chronic recurrent multifocal osteomyelitis with MR correlation: a case report.</strong>
|
|
Monatsschr. Kinderheilkd. 144: 1073-1077, 1996.
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</p>
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</div>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Spranger1965" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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|
Spranger, J. W., Paulsen, K., Lehmann, W.
|
|
<strong>Die kraniometaphysaere Dysplasie (Pyle).</strong>
|
|
Z. Kinderheilk. 93: 64-79, 1965.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14322785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14322785</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14322785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="15" class="mim-anchor"></a>
|
|
<a id="Taylor1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taylor, D. B., Sprague, P.
|
|
<strong>Dominant craniometaphyseal dysplasia: a family study over five generations.</strong>
|
|
Australas. Radiol. 33: 84-89, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2712793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2712793</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2712793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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[<a href="https://doi.org/10.1111/j.1440-1673.1989.tb03242.x" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="16" class="mim-anchor"></a>
|
|
<a id="Williams2003" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
|
|
Williams, C. J., Pendleton, A., Bonavita, G., Reginato, A. J., Hughes, A. E., Peariso, S., Doherty, M., McCarty, D. J., Ryan, L. M.
|
|
<strong>Mutations in the amino terminus of ANKH in two US families with calcium pyrophosphate dihydrate crystal deposition disease.</strong>
|
|
Arthritis Rheum. 48: 2627-2631, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13130483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13130483</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13130483" 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/10.1002/art.11133" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="17" class="mim-anchor"></a>
|
|
<a id="Williams2002" class="mim-anchor"></a>
|
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<div class="">
|
|
<p class="mim-text-font">
|
|
Williams, C. J., Zhang, Y., Timms, A., Bonavita, G., Caeiro, F., Broxholme, J., Cuthbertson, J., Jones, Y., Marchegiani, R., Reginato, A., Russell, R. G. G., Wordsworth, B. P., Carr, A. J., Brown, M. A.
|
|
<strong>Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH.</strong>
|
|
Am. J. Hum. Genet. 71: 985-991, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12297989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12297989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12297989[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=12297989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1086/343053" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
|
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
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<span class="mim-text-font">
|
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Matthew B. Gross - updated : 03/26/2014
|
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</span>
|
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</div>
|
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</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Patricia A. Hartz - updated : 3/25/2014<br>Marla J. F. O'Neill - updated : 11/9/2012<br>Cassandra L. Kniffin - updated : 11/10/2010<br>Victor A. McKusick - updated : 11/28/2006<br>Marla J. F. O'Neill - updated : 5/26/2004<br>Victor A. McKusick - updated : 5/3/2004<br>Victor A. McKusick - updated : 10/29/2002<br>Victor A. McKusick - updated : 11/14/2001<br>Victor A. McKusick - updated : 6/20/2001<br>Victor A. McKusick - updated : 4/18/2001
|
|
</span>
|
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</div>
|
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</div>
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</div>
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<div>
|
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<a id="creationDate" class="mim-anchor"></a>
|
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<div class="row">
|
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh : 7/13/2000
|
|
</span>
|
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</div>
|
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</div>
|
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</div>
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<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 09/12/2019
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
mgross : 03/26/2014<br>mgross : 3/26/2014<br>mcolton : 3/25/2014<br>carol : 11/12/2012<br>terry : 11/9/2012<br>wwang : 11/15/2010<br>ckniffin : 11/10/2010<br>alopez : 11/28/2006<br>terry : 11/28/2006<br>carol : 5/26/2004<br>carol : 5/26/2004<br>carol : 5/26/2004<br>terry : 5/26/2004<br>tkritzer : 5/10/2004<br>terry : 5/3/2004<br>carol : 11/1/2002<br>carol : 11/1/2002<br>tkritzer : 10/30/2002<br>terry : 10/29/2002<br>carol : 11/14/2001<br>carol : 11/14/2001<br>cwells : 7/2/2001<br>cwells : 6/25/2001<br>terry : 6/20/2001<br>alopez : 4/27/2001<br>terry : 4/18/2001<br>carol : 4/9/2001<br>joanna : 8/3/2000<br>alopez : 7/13/2000
|
|
</span>
|
|
</div>
|
|
</div>
|
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|
|
</div>
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</div>
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</div>
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</div>
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|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
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|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 605145
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ANKH INORGANIC PYROPHOSPHATE TRANSPORT REGULATOR; ANKH
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
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|
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<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
ANK, MOUSE, HOMOLOG OF<br />
|
|
HANK
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
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<div>
|
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<br />
|
|
</div>
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</div>
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<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: ANKH</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 5p15.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 5:14,704,800-14,871,778 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</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">
|
|
5p15.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Chondrocalcinosis 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
118600
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Craniometaphyseal dysplasia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
123000
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>ANKH is a highly conserved transmembrane pyrophosphate transporter that channels intracellular pyrophosphate into extracellular matrix, where it acts as a potent inhibitor of mineralization (Chen et al., 2011). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Mutation at the mouse 'progressive ankylosis' (ank) locus causes a generalized, progressive form of arthritis accompanied by mineral deposition, formation of bony outgrowths, and joint destruction. Ho et al. (2000) showed that the ank locus encodes a multipass transmembrane protein that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. Using a positional cloning approach, Ho et al. (2000) identified the mouse Ank gene. Using the exon/intron structure of the mouse gene and partial sequence from human EST clones, Ho et al. (2000) amplified and sequenced the complete coding region of human ANK. Orthologs of mouse Ank were also found in zebrafish, rat, and cow. The human ANK gene is virtually identical to mouse ank, with only 9 amino acid differences over a 492-amino acid protein. There are 3 potential N-linked glycosylation sites and multiple putative phosphorylation sites. A hydropathy analysis revealed 9 to 12 hydrophobic stretches, most approximately 20 residues long, as would be expected for membrane-spanning regions in an integral multipass transmembrane protein. Western blot analysis suggested that the ank protein is expressed at the cell surface. Northern blot analysis revealed that ank mRNA is expressed in many tissues in adult mice, including heart, brain, liver, spleen, lung, muscle, and kidney. </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Although soft tissue phenotypes had not been reported in ank mice, Ho et al. (2000) observed increased calcification in kidneys of adult mice, consistent with an important role for the gene in nonskeletal tissues. Fibroblasts from ank mutants displayed about a 2-fold increase in intracellular inorganic pyrophosphate levels over wildtype cells and there was a 3- to 5-fold decrease in extracellular pyrophosphate levels. Additional studies demonstrated that ANK functions through a probenecid-sensitive anion transport mechanism. Ho et al. (2000) suggested that these results identified ANK-mediated control of pyrophosphate levels as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>By radiation hybrid mapping, Ho et al. (2000) mapped the human ANK gene to chromosome 5p, in a region showing homology of synteny with proximal mouse chromosome 15. </p><p>Nurnberg et al. (2001) stated that the ANKH gene maps to chromosome 5p15.2-p14.1. </p><p>Gross (2014) mapped the ANKH gene to chromosome 5p15.2 based on an alignment of the ANKH sequence (GenBank AF274753) with the genomic sequence (GRCh37).</p>
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<div>
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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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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Craniometaphyseal Dysplasia</em></strong></p><p>
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Craniometaphyseal dysplasia is a bone dysplasia characterized by overgrowth and sclerosis of the craniofacial bones and abnormal modeling of the metaphyses of the tubular bones. Hyperostosis and sclerosis of the skull may lead to cranial nerve compressions resulting in hearing loss and facial palsy. An autosomal dominant form of the disorder (CMDD; 123000) was mapped to 5p15.2-p14.1 (Nurnberg et al., 1997) within a region harboring the human homolog (ANKH) of the mouse progressive ankylosis (ank) gene. The ANK protein spans the outer cell membrane and shuttles inorganic pyrophosphate, a major inhibitor of physiologic and pathologic calcification, bone mineralization, and bone resorption. Nurnberg et al. (2001) identified 6 different heterozygous mutations in the ANKH gene in 8 of 9 families with CMDD (see, e.g., 605145.0001-605145.0005). The mutations predicted single amino acid substitutions, deletions, or insertions. Using a helix prediction program, they proposed for the ANK molecule 12 membrane-spanning helices with an alternate inside/out orientation and a central channel permitting the passage of inorganic pyrophosphate. The mutations occurred at highly conserved amino acid residues presumed to be located in the cytosolic portion of the protein. The results linked the inorganic pyrophosphate channel ANK with bone formation and remodeling. </p><p>Reichenberger et al. (2001) demonstrated 3 different mutations in the ANKH gene in 5 different families and in isolated cases of CMDD. All mutations clustered within 7 amino acids in 1 of the 6 possible cytosolic domains of the ANKH protein. These results suggested that the mutated protein has a dominant-negative effect on its function, since reduced levels of pyrophosphate in bone matrix increase mineralization. Progressive thickening and increased mineral density of craniofacial bones and abnormally developed metaphyses in the long bones characterize CMD. </p><p><strong><em>Chondrocalcinosis-2</em></strong></p><p>
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|
Chondrocalcinosis is a common cause of joint pain and arthritis that is caused by the deposition of calcium-containing crystals within articular cartilage. Pendleton et al. (2002) showed that affected members of 2 previously described families with chondrocalcinosis-2 (CCAL2; 118600), which is also called calcium pyrophosphate dihydrate deposition disease (CPPDD), had mutations in the ANKH gene. One of the mutations resulted in the substitution of a highly conserved amino acid residue within a predicted transmembrane segment (605145.0006); the other created a new ATG start site that added 4 additional residues to the ANKH protein (605145.0007). In addition, 1 of 95 patients with sporadic chondrocalcinosis from the U.K. showed a deletion of a single codon in the ANKH gene (605145.0008). The same change was found in the patient's sister and son; the sister had bilateral knee replacement for osteoarthritis. Each of the 3 mutations was reconstructed in a full-length ANK expression construct previously shown to regulate pyrophosphate levels in cultured cells in vitro. All 3 mutations showed significantly more activity than a previously described nonsense mutation that causes severe hydroxyapatite mineral deposition and widespread joint ankylosis in mice. These results suggested that small sequence changes in ANKH are 1 cause of chondrocalcinosis and joint disease in humans. Increased ANK activity may explain the different types of crystals commonly deposited in CCAL2 families and mutant mice, and may provide a useful pharmacologic target for treating some forms of human chondrocalcinosis. </p><p>In a family with calcium pyrophosphate dihydrate deposition disease, Williams et al. (2002) identified a pro5-to-leu (605145.0009) mutation in the ANKH gene. They postulated that loss of function of ANKH causes elevated extracellular inorganic pyrophosphate levels, predisposing to CCAL2 crystal deposition. </p><p>Williams et al. (2003) screened for mutations in the ANKH gene in 2 U.S. families with autosomal dominant CPPDD and found that all affected members were heterozygous for a pro5-to-thr mutation (605145.0010). The 2 families displayed distinct haplotypes. Williams et al. (2003) noted that the family described by Williams et al. (2002) had a different mutation at the same codon (see 605145.0009) and also displayed a distinct haplotype. They concluded that the evolutionarily conserved pro5 position of ANKH may represent a hotspot for mutation in families with autosomal dominant CCAL2. </p><p>Mutations in the progressive ankylosis gene (Ank/ANKH) cause surprisingly different skeletal phenotypes in mice and humans. Ank encodes a multiple-pass transmembrane protein that regulates pyrophosphate levels inside and outside tissue culture cells; conflicting models have been proposed to explain the effects of the human mutations. Gurley et al. (2006) tested wildtype and mutant forms of ANK for radiolabeled pyrophosphate-transport activity in frog oocytes. They also reconstructed 2 human mutations in a bacterial artificial chromosome and tested them in transgenic mice for rescue of the Ank-null phenotype and for induction of new skeletal phenotypes. Wildtype ANK stimulates saturable transport of pyrophosphate ions across the plasma membrane, with half maximal rates attained at physiologic levels of pyrophosphate. Chondrocalcinosis mutations retain apparently wildtype transport activity and can rescue the joint-fusion phenotype of Ank-null mice. Craniometaphyseal dysplasia mutations do not transport pyrophosphate and cannot rescue the defects of Ank-null mice. Furthermore, microcomputed tomography revealed previously unappreciated phenotypes in Ank-null mice that are reminiscent of craniometaphyseal dysplasia. The combination of biochemical and genetic analyses provided insight into how mutations in ANKH cause human skeletal disease. </p><p>In an Australian family with CMDD and a known mutation in the ANKH gene (G389R; 605145.0002), Baynam et al. (2009) found evidence for chondrocalcinosis segregating with CMDD in mutation-positive female family members. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Mice carrying the progressive ankylosis mutation have been studied as a model of arthritis. The autosomal recessive Ank mutation causes an abnormal flat-footed gait in young mice due to decreased mobility of ankle and toe joints. Loss of joint mobility becomes more severe with age and spreads to most joints throughout the limbs and vertebral column leading to complete rigidity and death around 6 months of age. Hydroxyapatite crystals develop in articular surfaces and synovial fluid of Ank mice, accompanied by joint space narrowing, cartilage erosion, and formation of bony outgrowths or osteophytes that cause fusion (ankylosis) and joint immobility. Ho et al. (2000) identified a G-to-T substitution in the mouse Ank gene, leading to a nonsense mutation in exon 11, the penultimate exon of mouse Ank. This mutation truncates the C-terminal region of the protein and greatly reduces its activity in vitro. The mouse Ank gene is expressed in developing articular surfaces and may help maintain the unmineralized state by providing a local source of inorganic pyrophosphate to inhibit hydroxyapatite formation. In the absence of normal Ank activity, mineralization extends unhindered throughout articular cartilage, hydroxyapatite deposits form in synovial fluid, and new bone is deposited in and around joints, showing that the gene is essential for normal joint maintenance. </p><p>Chen et al. (2011) created knockin (KI) mice overexpressing human ANK with the phe377 deletion (605145.0001) associated with craniometaphyseal dysplasia. Ank KI/KI mice exhibited increased bone mass in craniofacial bones, especially in mandibles, excessive trabecular bone in diaphyses of long bones, and hypomineralization of cortex of long bones. Metaphyses were undertrabeculated. Cultured Ank KI/KI calvarial osteoblasts and bone marrow stromal cells showed reduced mineral nodule formation compared with wildtype controls. Mature osteoclasts derived from Ank KI/KI bone marrow progenitors were reduced in size, showed a disrupted actin ring, produced fewer multinucleated osteoclasts, and displayed reduced cell migration. Extracellular pyrophosphate was normal in Ank KI/KI osteoblasts, apparently due to compensatory upregulation of Pc1 (ENPP1; 173335), another regulator of extracellular pyrophosphate. Chen et al. (2011) found that peripheral blood mononuclear cells of adult craniometaphyseal dysplasia patients also showed defective osteoclastogenesis, with reduced number of multinucleated osteoclasts and reduced mineral resorption. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>13 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 CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ANKH, PHE377DEL
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<br />
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SNP: rs121908405,
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ClinVar: RCV000005501, RCV001851667, RCV002247252
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In 2 apparently unrelated German families with craniometaphyseal dysplasia (123000), previously reported by Spranger et al. (1965) and Schwahn et al. (1996), Nurnberg et al. (2001) found deletion of 3 basepairs leading to deletion of codon 377 (phenylalanine). Because of different haplotype backgrounds, these were thought to be recurrent mutations, an interpretation favored by a short tandem repeat structure for F377del (1196delCTT). </p><p>Reichenberger et al. (2001) reported the same mutation in affected members of 2 families with craniometaphyseal dysplasia. They designated the mutation PHE376DEL (1127delTCT) based on a different numbering system. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0002 CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
|
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CHONDROCALCINOSIS 2, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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ANKH, GLY389ARG
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<br />
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SNP: rs28939080,
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ClinVar: RCV000005502, RCV000032998
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a Swiss family and an Australian family with craniometaphyseal dysplasia (CMDD; 123000), the latter family originally reported by Taylor and Sprague (1989), Nurnberg et al. (2001) identified a gly389-to-arg (G389R) missense mutation in the ANKH gene as the basis of craniometaphyseal dysplasia. That these were recurrent mutations was supported by the fact that they were on different haplotype backgrounds and by the nature of the affected sequence, namely, a CpG dinucleotide for G389R (1233G-A). </p><p>Baynam et al. (2009) restudied the Australian family with CMDD that was originally reported by Taylor and Sprague (1989) and found evidence for chondrocalcinosis segregating with CMDD in mutation-positive female family members. Although a chance association of chondrocalcinosis with CMDD could not be excluded, Baynam et al. (2009) suggested that the lack of joint symptoms in affected male family members might be due to involvement of sex-dependent mechanisms or to the fact that only mutation-positive women in the pedigree had reached the age at which the chondrocalcinosis phenotype typically expresses. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0003 CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ANKH, IVS9, A-G, -4
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<br />
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SNP: rs1579998709,
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ClinVar: RCV000005503, RCV001851668
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with craniometaphyseal dysplasia (123000), Nurnberg et al. (2001) identified an insertion of a single alanine in the ANKH cDNA; the mutation, however, was an A-to-G transition in the splice acceptor site of intron 9 that ended with a split codon, which contributed to the codon (GCA) for the extra alanine. A new splice acceptor site in the disease allele was created by the heterozygous point mutation at position -4 of the splice donor site of intron 9. Reichenberger et al. (2001) identified the same mutation in affected members of a family with craniometaphyseal dysplasia. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-text-font">
|
|
<strong>.0004 MOVED TO 605145.0001</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0005 CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
|
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</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ANKH, SER375DEL
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<br />
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|
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SNP: rs121908406,
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ClinVar: RCV000005504, RCV001090992
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 2 affected members of a family with craniometaphyseal dysplasia (123000), Nurnberg et al. (2001) identified a 3-bp deletion (1192delCTT) in exon 9 of the ANKH gene, resulting in the deletion of ser375. In 2 sporadic cases of craniometaphyseal dysplasia, Reichenberger et al. (2001) found the same 3-bp deletion, which they designated 1122delCTC based on a different numbering system. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0006 CHONDROCALCINOSIS 2</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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|
ANKH, MET48THR
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<br />
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|
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SNP: rs121908407,
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ClinVar: RCV000005505
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
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<p>In a French family with chondrocalcinosis-2 (118600) reported by Andrew et al. (1999), Pendleton et al. (2002) found that affected members were heterozygous for a 143T-C transition in exon 2 of the ANKH gene, resulting in a met48-to-thr (M48T) substitution. The mutation is in a transmembrane domain at a position that is absolutely conserved in the ANKH protein over 400 million years of evolution from fish to mammals. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0007 CHONDROCALCINOSIS 2</strong>
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</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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ANKH, -11C-T
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<br />
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|
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SNP: rs2126640512,
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|
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ClinVar: RCV000005506
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a British family with chondrocalcinosis-2 (118600) reported by Hughes et al. (1995), Pendleton et al. (2002) found that affected members were heterozygous for a -11C-T change located 11-bp upstream of the normal ATG initiation codon of the ANKH gene. This change generated an alternative ATG initiation codon and added 4 amino acids to the highly conserved N terminus of the ANKH protein. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0008 CHONDROCALCINOSIS 2, SPORADIC</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ANKH, GLU490DEL
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<br />
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|
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SNP: rs121908408,
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|
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gnomAD: rs121908408,
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ClinVar: RCV000005507
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In 1 of 95 British patients with sporadic chondrocalcinosis-2 (118600), Pendleton et al. (2002) identified a 3-bp deletion in exon 12 of the ANKH gene that deleted a glutamate residue (E490del) located 3 amino acids from the highly conserved C terminus of the ANKH protein. The 79-year-old proband had a sister who had undergone bilateral knee replacements for 'osteoarthritis.' The sister and son of the proband were heterozygous for this ANKH mutation, but the son was not yet old enough for a reliable diagnosis of chondrocalcinosis. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0009 CHONDROCALCINOSIS 2</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ANKH, PRO5LEU
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<br />
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SNP: rs121908409,
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ClinVar: RCV000005508, RCV004719627
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with autosomal dominant familial calcium pyrophosphate dihydrate deposition disease (118600), Williams et al. (2002) identified a C-to-T transition at 14 bp from the start codon of the ANKH gene, resulting in a pro5-to-leu (P5L) change, which segregated with the disease. Some members of the family with the disease haplotype were considered too young to manifest the disorder; some other members of the family did not have the disease haplotype but were apparently affected. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0010 CHONDROCALCINOSIS 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ANKH, PRO5THR
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<br />
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SNP: rs121908410,
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ClinVar: RCV000005509, RCV004734498
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Williams et al. (2003) screened 2 US families with autosomal dominant calcium pyrophosphate dihydrate deposition disease (118600) for mutations in the ANKH gene and found that all affected members were heterozygous for a pro5-to-thr (P5T) mutation. They noted that another mutation at the same codon (P5L; 605145.0009) had previously been reported to cause the same disorder and suggested that the evolutionarily conserved P5 position of ANKH may represent a hotspot for mutation in families with autosomal dominant CPPDD. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0011 CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ANKH, CYS339ARG
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<br />
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SNP: rs267606656,
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ClinVar: RCV000005510
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a French boy with craniometaphyseal dysplasia (123000), Kornak et al. (2010) identified a heterozygous 1015T-C transition in exon 9 of the ANKH gene, resulting in a cys339-to-arg (C339R) substitution in a highly conserved residue in transmembrane helix 9. The patient had a severe form of the disorder, with hearing loss and bilateral facial palsy developing soon after birth. He had severe sclerosis of the skull base, orbits, maxilla, and mandible, with almost complete obstruction of the sinuses. There was rapid worsening of the bone phenotype in the first years of life. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0012 CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ANKH, LEU391PRO
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<br />
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SNP: rs267606658,
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ClinVar: RCV000005511
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 24-year-old man from the Netherlands with craniometaphyseal dysplasia (123000), Kornak et al. (2010) identified a heterozygous 1172T-C transition in exon 10 of the ANKH gene, resulting in a leu391-to-pro (L391P) substitution in a highly conserved residue in the loop between transmembrane helices 10 and 11. The patient presented with progressive conductive and sensorineural hearing loss and was found to have typical features of the disorder, with unilateral facial palsy apparent in infancy, macrocephaly, and teeth crowding. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0013 CRANIOMETAPHYSEAL DYSPLASIA, AUTOSOMAL DOMINANT</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ANKH, LEU334ARG
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<br />
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SNP: rs267606657,
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ClinVar: RCV000005512
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 43-year-old Italian man with craniometaphyseal dysplasia (123000), Kornak et al. (2010) identified a heterozygous 1001T-G transversion in exon 8 of the ANKH gene, resulting in a leu334-to-arg (L334R) substitution in a highly conserved residue in transmembrane helix 9. The patient had typical manifestations of CMD, with sclerosis of the skull base and maxilla, hyperostotic but not sclerotic mandible, and partially obstructed sinuses without cranial nerve compression. He also had narrowing of the middle ear cavities with bilateral fixation of the body of the incus to the lateral attic, resulting in conductive deafness and tinnitus. These middle ear manifestations were similar to those observed in postinflammatory ossicular fixation secondary to acute or chronic otitis media. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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|
Andrew, L. J., Brancolini, V., Serrano de la Pena, L., Devoto, M., Caeiro, F., Marchegiani, R., Reginato, A., Gaucher, A., Netter, P., Gillet, P., Loeuille, D., Prockop, D. J., Carr, A., Wordsworth, B. F., Lathrop, M., Butcher, S., Considine, E., Everts, K., Nicod, A., Walsh, S., Williams, C. J.
|
|
<strong>Refinement of the chromosome 5p locus for familial calcium pyrophosphate dihydrate deposition disease.</strong>
|
|
Am. J. Hum. Genet. 64: 136-145, 1999.
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|
|
[PubMed: 9915952]
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[Full Text: https://doi.org/10.1086/302186]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Baynam, G., Goldblatt, J., Schofield, L.
|
|
<strong>Craniometaphyseal dysplasia and chondrocalcinosis cosegregating in a family with an ANKH mutation. (Letter)</strong>
|
|
Am. J. Med. Genet. 149A: 1331-1333, 2009.
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|
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|
|
[PubMed: 19449425]
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[Full Text: https://doi.org/10.1002/ajmg.a.32875]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Chen, I.-P., Wang, L., Jiang, X., Aguila, H. L., Reichenberger, E. J.
|
|
<strong>A Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD).</strong>
|
|
Hum. Molec. Genet. 20: 948-961, 2011.
|
|
|
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|
|
[PubMed: 21149338]
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[Full Text: https://doi.org/10.1093/hmg/ddq541]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 3/26/2014.
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|
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Gurley, K. A., Reimer, R. J., Kingsley, D. M.
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|
<strong>Biochemical and genetic analysis of ANK in arthritis and bone disease.</strong>
|
|
Am. J. Hum. Genet. 79: 1017-1029, 2006.
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|
|
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|
|
[PubMed: 17186460]
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[Full Text: https://doi.org/10.1086/509881]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Ho, A. M., Johnson, M. D., Kingsley, D. M.
|
|
<strong>Role of the mouse ank gene in control of tissue calcification and arthritis.</strong>
|
|
Science 289: 265-270, 2000.
|
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|
|
[PubMed: 10894769]
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|
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[Full Text: https://doi.org/10.1126/science.289.5477.265]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Hughes, A. E., McGibbon, D., Woodward, E., Dixey, J., Doherty, M.
|
|
<strong>Localisation of a gene for chondrocalcinosis to chromosome 5p.</strong>
|
|
Hum. Molec. Genet. 4: 1225-1228, 1995.
|
|
|
|
|
|
[PubMed: 8528213]
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|
|
[Full Text: https://doi.org/10.1093/hmg/4.7.1225]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Kornak, U., Brancati, F., Le Merrer, M., Lichtenbelt, K., Hohne, W., Tinschert, S., Garaci, F. G., Dallapiccola, B., Nurnberg, P.
|
|
<strong>Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss.</strong>
|
|
Am. J. Med. Genet. 152A: 870-874, 2010.
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|
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|
|
[PubMed: 20358596]
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|
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[Full Text: https://doi.org/10.1002/ajmg.a.33301]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Nurnberg, P., Thiele, H., Chandler, D., Hohne, W., Cunningham, M. L., Ritter, H., Leschik, G., Uhlmann, K., Mischung, C., Harrop, K., Goldblatt, J., Borochowitz, Z. U., Kotzot, D., Westermann, F., Mundlos, S., Braun, H.-S., Laing, N., Tinschert, S.
|
|
<strong>Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.</strong>
|
|
Nature Genet. 28: 37-41, 2001.
|
|
|
|
|
|
[PubMed: 11326272]
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|
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[Full Text: https://doi.org/10.1038/ng0501-37]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Nurnberg, P., Tinschert, S., Mrug, M., Hampe, J., Muller, C. R., Fuhrmann, E., Braun, H.-S., Reis, A.
|
|
<strong>The gene for autosomal dominant craniometaphyseal dysplasia maps to chromosome 5q and is distinct from the growth hormone-receptor gene.</strong>
|
|
Am. J. Hum. Genet. 61: 918-923, 1997.
|
|
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|
|
|
[PubMed: 9382103]
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|
|
[Full Text: https://doi.org/10.1086/514880]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Pendleton, A., Johnson, M. D., Hughes, A., Gurley, K. A., Ho, A. M., Doherty, M., Dixey, J., Gillet, P., Loeuille, D., McGrath, R., Reginato, A., Shiang, R., Wright, G., Netter, P., Williams, C., Kingsley, D. M.
|
|
<strong>Mutations in ANKH cause chondrocalcinosis.</strong>
|
|
Am. J. Hum. Genet. 71: 933-940, 2002.
|
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|
[PubMed: 12297987]
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|
|
[Full Text: https://doi.org/10.1086/343054]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Reichenberger, E., Tiziani, V., Watanabe, S., Park, L., Ueki, Y., Santanna, C., Baur, S. T., Shiang, R., Grange, D. K., Beighton, P., Gardner, J., Hamersma, H., Sellars, S., Ramesar, R., Lidral, A. C., Sommer, A., Raposo do Amaral, C. M., Gorlin, R. J., Mulliken, J. B., Olsen, B. R.
|
|
<strong>Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK.</strong>
|
|
Am. J. Hum. Genet. 68: 1321-1326, 2001.
|
|
|
|
|
|
[PubMed: 11326338]
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|
|
[Full Text: https://doi.org/10.1086/320612]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Schwahn, B., Schaper, J., Herkenrath, P., Michel, O., Schonau, E.
|
|
<strong>Chronic recurrent multifocal osteomyelitis with MR correlation: a case report.</strong>
|
|
Monatsschr. Kinderheilkd. 144: 1073-1077, 1996.
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|
|
</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Spranger, J. W., Paulsen, K., Lehmann, W.
|
|
<strong>Die kraniometaphysaere Dysplasie (Pyle).</strong>
|
|
Z. Kinderheilk. 93: 64-79, 1965.
|
|
|
|
|
|
[PubMed: 14322785]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Taylor, D. B., Sprague, P.
|
|
<strong>Dominant craniometaphyseal dysplasia: a family study over five generations.</strong>
|
|
Australas. Radiol. 33: 84-89, 1989.
|
|
|
|
|
|
[PubMed: 2712793]
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|
|
[Full Text: https://doi.org/10.1111/j.1440-1673.1989.tb03242.x]
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</p>
|
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</li>
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<li>
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<p class="mim-text-font">
|
|
Williams, C. J., Pendleton, A., Bonavita, G., Reginato, A. J., Hughes, A. E., Peariso, S., Doherty, M., McCarty, D. J., Ryan, L. M.
|
|
<strong>Mutations in the amino terminus of ANKH in two US families with calcium pyrophosphate dihydrate crystal deposition disease.</strong>
|
|
Arthritis Rheum. 48: 2627-2631, 2003.
|
|
|
|
|
|
[PubMed: 13130483]
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|
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|
|
[Full Text: https://doi.org/10.1002/art.11133]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Williams, C. J., Zhang, Y., Timms, A., Bonavita, G., Caeiro, F., Broxholme, J., Cuthbertson, J., Jones, Y., Marchegiani, R., Reginato, A., Russell, R. G. G., Wordsworth, B. P., Carr, A. J., Brown, M. A.
|
|
<strong>Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH.</strong>
|
|
Am. J. Hum. Genet. 71: 985-991, 2002.
|
|
|
|
|
|
[PubMed: 12297989]
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|
[Full Text: https://doi.org/10.1086/343053]
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</p>
|
|
</li>
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</ol>
|
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<div>
|
|
<br />
|
|
</div>
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|
</div>
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</div>
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<div>
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|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Matthew B. Gross - updated : 03/26/2014<br>Patricia A. Hartz - updated : 3/25/2014<br>Marla J. F. O'Neill - updated : 11/9/2012<br>Cassandra L. Kniffin - updated : 11/10/2010<br>Victor A. McKusick - updated : 11/28/2006<br>Marla J. F. O'Neill - updated : 5/26/2004<br>Victor A. McKusick - updated : 5/3/2004<br>Victor A. McKusick - updated : 10/29/2002<br>Victor A. McKusick - updated : 11/14/2001<br>Victor A. McKusick - updated : 6/20/2001<br>Victor A. McKusick - updated : 4/18/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
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<br />
|
|
</div>
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<div>
|
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<div class="row">
|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh : 7/13/2000
|
|
</span>
|
|
</div>
|
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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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