View source for 7sij


==Myocilin OLF mutant E352K==
<StructureSection load='7sij' size='340' side='right'caption='[[7sij]], [[Resolution|resolution]] 1.54&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7sij]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SIJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SIJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.54&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7sij FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sij OCA], [https://pdbe.org/7sij PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sij RCSB], [https://www.ebi.ac.uk/pdbsum/7sij PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sij ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Accurate predictions of the pathogenicity of mutations associated with genetic diseases are key to the success of precision medicine. Inherited missense mutations in the myocilin (MYOC) gene, within its olfactomedin (OLF) domain, constitute the strongest genetic link to primary open-angle glaucoma via a toxic gain of function, and thus MYOC is an attractive precision-medicine target. However, not all mutations in MYOC cause glaucoma, and common variants are expected to be neutral polymorphisms. The Genome Aggregation Database (gnomAD) lists approximately 100 missense variants documented within OLF, all of which are relatively rare (allele frequency &lt;0.001%) and nearly all are of unknown pathogenicity. To distinguish disease-causing OLF variants from benign OLF variants, we first characterized the most prevalent population-based variants using a suite of cellular and biophysical assays, and identified two variants with features of aggregation-prone familial disease variants. Next, we considered all available biochemical and clinical data to demonstrate that pathogenic and benign variants can be differentiated statistically based on a single metric: the thermal stability of OLF. Our results motivate genotyping MYOC in patients for clinical monitoring of this widespread, painless and irreversible ocular disease.

Quantitative differentiation of benign and misfolded glaucoma-causing myocilin variants on the basis of protein thermal stability.,Scelsi HF, Hill KR, Barlow BM, Martin MD, Lieberman RL Dis Model Mech. 2023 Jan 1;16(1):dmm049816. doi: 10.1242/dmm.049816. Epub 2023 , Jan 13. PMID:36579626<ref>PMID:36579626</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7sij" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Barlow BM]]
[[Category: Lieberman RL]]
[[Category: Scelsi HS]]