23
DOI: https://doi.org/10.1186/s43141-023-00551-4
English
eng
Ajith, Athira
Contributor
<p><ul id="issue-navigation" class="issue-navigation u-margin-s-bottom u-bg-grey1" style="box-sizing: border-box; margin-top: 0px; margin-right: 0px; margin-bottom: 16px !important; margin-left: 0px; padding: 0px; list-style: none; background-color: rgb(245, 245, 245) !important; overflow: hidden; font-size: 16px; line-height: 24px; color: rgb(31, 31, 31); font-family: ElsevierSans, Arial, Helvetica, Roboto, "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", STIXGeneral, "Cambria Math", "Arial Unicode MS", sans-serif; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; white-space: normal; text-decoration-thickness: initial; text-decoration-style: initial; text-decoration-color: initial;"><li class="previous move-left u-padding-s-ver u-padding-s-left" style="box-sizing: border-box; margin: 0px; padding-top: 16px !important; padding-right: 0px; padding-bottom: 16px !important; padding-left: 16px !important; float: left; left: 0px;"><a class="button-alternative button-alternative-tertiary u-display-flex button-alternative-icon-left" href="https://www.sciencedirect.com/science/article/pii/S1687157X23010260" style="box-sizing: border-box; margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; --sd-ui-button-alt-border-bottom-colour: transparent; --sd-ui-button-alt-border-bottom-colour-hover: #eb6500; --sd-ui-button-alt-border-bottom-width: 2px; --sd-ui-button-alt-colour: #1f1f1f; --sd-ui-button-alt-colour-focus: #eb6500; --sd-ui-button-alt-cursor: pointer; --sd-ui-button-alt-font-size: 1em; --sd-ui-button-alt-gap: calc(0.5em - 2px); --sd-ui-button-alt-min-width: 5.5rem; --sd-ui-button-alt-icon-background-colour: transparent; --sd-ui-button-alt-icon-background-colour-hover: transparent; --sd-ui-button-alt-icon-border-colour: #1f1f1f; --sd-ui-button-alt-icon-border-colour-hover: #eb6500; --sd-ui-button-alt-icon-fill: #1f1f1f; --sd-ui-button-alt-icon-fill-hover: #1f1f1f; --sd-ui-button-alt-icon-padding: 0.5rem; --sd-ui-button-alt-icon-size: 2.5rem; --sd-ui-button-alt-icon-external-link-size: 0.625rem; -webkit-box-align: baseline; align-items: baseline; border: none; color: rgb(31, 31, 31); cursor: pointer; display: flex !important; font-family: inherit; font-size: 16px; gap: 6px; line-height: 24px; min-width: 88px; text-decoration: none; user-select: text;"><svg focusable="false" viewBox="0 0 54 128" height="20" class="icon icon-navigate-left"><path d="M1 61l45-45 7 7-38 38 38 38-7 7z"></path></svg></a></li></ul></p><div class="Abstracts u-font-serif" id="abstracts" style="box-sizing: border-box; margin: 0px; padding: 0px; --sd-ui-line-height: calc(1em + 10px); line-height: 26px; font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif !important; color: rgb(31, 31, 31); font-size: 16px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; white-space: normal; text-decoration-thickness: initial; text-decoration-style: initial; text-decoration-color: initial;"><div class="abstract author" id="ab0005" style="box-sizing: border-box; margin: 0px 0px 8px; padding: 0px;"><div id="abs0005" style="box-sizing: border-box; margin: 0px; padding: 0px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="sect0010" style="box-sizing: border-box; margin-top: 24px !important; margin-right: 0px; margin-bottom: 8px !important; margin-left: 0px; padding: 0px; font-weight: normal !important; font-size: 20px !important; line-height: 30px !important;">Background</h3><div class="u-margin-s-bottom" id="sp0065" style="box-sizing: border-box; margin-top: 0px; margin-right: 0px; margin-bottom: 16px !important; margin-left: 0px; padding: 0px;">Tuftelin 1 (<em style="box-sizing: border-box; margin: 0px; padding: 0px;">TUFT1</em><span style="box-sizing: border-box; margin: 0px; padding: 0px;">) gene is important in the development and<span> </span><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/mineralization" class="topic-link" style="box-sizing: border-box; margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">mineralization</a><span> </span>of dental enamel. The study aimed to identify potential functionally deleterious non-synonymous SNPs (nsSNPs) in the<span> </span></span><em style="box-sizing: border-box; margin: 0px; padding: 0px;">TUFT1</em><span style="box-sizing: border-box; margin: 0px; padding: 0px;"><span style="box-sizing: border-box; margin: 0px; padding: 0px;"><span style="box-sizing: border-box; margin: 0px; padding: 0px;"><span> </span>gene by using different in silico tools. The deleterious<span> </span><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/missense" class="topic-link" style="box-sizing: border-box; margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">missense</a><span> </span>SNPs were identified from SIFT, PolyPhen-2, PROVEAN, SNPs & GO,<span> </span></span><a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/protein-characterization" class="topic-link" style="box-sizing: border-box; margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">PANTHER</a>, and SNAP2. The stabilization, conservation, and three-dimensional modeling of<span> </span></span><a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/mutant-protein" class="topic-link" style="box-sizing: border-box; margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">mutant proteins</a><span> </span>were analyzed by I-Mutant 3.0, Consurf, and Project HOPE, respectively. The protein–protein interaction using STRING, GeneMANIA for gene–gene interaction, and DynaMut for evaluating the impact of the mutation on protein stability, conformation, and flexibility.</span></div></div><div id="abs0010" style="box-sizing: border-box; margin: 0px; padding: 0px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="sect0015" style="box-sizing: border-box; margin-top: 24px !important; margin-right: 0px; margin-bottom: 8px !important; margin-left: 0px; padding: 0px; font-weight: normal !important; font-size: 20px !important; line-height: 30px !important;">Results</h3><div class="u-margin-s-bottom" id="sp0070" style="box-sizing: border-box; margin-top: 0px; margin-right: 0px; margin-bottom: 16px !important; margin-left: 0px; padding: 0px;"><span style="box-sizing: border-box; margin: 0px; padding: 0px;">Eight deleterious nsSNPs (E242A, R303W, K182N, K123N, R117W, H289Q, R203W, and Q107R) out of 304 were found to have high-risk damaging effects using six in silico tools. Among them, K182N and K123N alone had increased stability, whereas E242A, R303W, R117W, H289Q, Q107R, and R203W exhibited a decrease in protein stability, based on DDG values. Meanwhile, all the eight deleterious nsSNPs altered the size, charge,<span> </span><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/hydrophobicity" class="topic-link" style="box-sizing: border-box; margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">hydrophobicity</a><span style="box-sizing: border-box; margin: 0px; padding: 0px;">, and spatial organization of the<span> </span><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/amino-acids" class="topic-link" style="box-sizing: border-box; margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">amino acids</a><span style="box-sizing: border-box; margin: 0px; padding: 0px;"><span> </span>and predominantly had<span> </span><a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/alpha-helix" class="topic-link" style="box-sizing: border-box; margin: 0px; padding: 0px; background-color: rgba(0, 0, 0, 0); word-break: break-word; text-decoration: underline 1px rgb(31, 31, 31); color: rgb(31, 31, 31); text-underline-offset: 1px;">alpha helix</a><span> </span>domains. These deleterious variants were located in highly conserved regions except R203W. Protein–protein interaction predicted that TUFT1 interacted with ten proteins that are involved in enamel mineralization and odontogenesis. Gene–gene interaction network showed that<span> </span></span></span></span><em style="box-sizing: border-box; margin: 0px; padding: 0px;">TUFT1</em><span> </span>is involved in physical interactions, gene co-localization, and pathway interactions. DynaMut ΔΔG values predicted that five nsSNPs were destabilizing the protein, ΔΔG ENCoM values showed a destabilizing effect for all mutants, and seven nsSNPs increased the molecular flexibility of TUFT1.</div></div><div id="abs0015" style="box-sizing: border-box; margin: 0px; padding: 0px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="sect0020" style="box-sizing: border-box; margin-top: 24px !important; margin-right: 0px; margin-bottom: 8px !important; margin-left: 0px; padding: 0px; font-weight: normal !important; font-size: 20px !important; line-height: 30px !important;">Conclusion</h3><div class="u-margin-s-bottom" id="sp0075" style="box-sizing: border-box; margin-top: 0px; margin-right: 0px; margin-bottom: 16px !important; margin-left: 0px; padding: 0px;">Our study predicted eight functional SNPs that had detrimental effects on the structure and function of the<span> </span><em style="box-sizing: border-box; margin: 0px; padding: 0px;">TUFT1</em><span> </span>gene. This will aid in the development of candidate deleterious markers as a potential target for disease diagnosis and therapeutic interventions.</div></div></div></div>
Elsevier
December 2023
pdf
Journal of Genetic Engineering and Biotechnology
In silico screening of non-synonymous SNPs in human TUFT1 gene
mixed material
Elsevier