@article{article_571528, title={Assessing the Functional Properties of the TMCO1 Sequence Variants by Using In Silico Analyses}, journal={Duzce University Journal of Science and Technology}, volume={7}, pages={1931–1946}, year={2019}, DOI={10.29130/dubited.571528}, author={Pirim, Dilek and Ulusoy, Erva and Kurt, Zeynep and Kaya, Niyazi and Uz-yıldırım, Elif}, keywords={TMCO1,Cerebro-facio-thoracic dysplasia,RegulomeDB,SNV,post-translational modifications,in silico analyses}, abstract={<p class="MsoNormal" style="margin-bottom:.0001pt;text-align:justify;"> <span style="font-size:10pt;line-height:115%;font-family:’Times New Roman’, serif;">Transmembrane
and Coiled-Coil Domains 1 (TMCO1) protein is encoded by <i>TMCO1 </i> gene consists of 7 exons. Previous studies have identified
multiple <i>TMCO1 </i> variants in patients
with cerebro-facio-thoracic dysplasia (CFTD) and <i>TMCO1 </i> locus was also shown to be associated with primary open angle
glaucoma (POAG). However, there are limited number of research exist reporting
associations of the <i>TMCO1 </i> gene
sequence variants and majority of the findings affirm the pathogenicity of the
nonsense and frameshift <i>TMCO1 </i> variants
and their associations with clinical phenotypes. Thus functional properties of
the single nucleotide variants causing amino acid changes in the TMCO1 are yet
to be comprehensively elucidated. In this study, we evaluated the effects of
amino acid substitutions on protein structure, identified their putative roles
in post-translational modifications (PTM) and in regulatory mechanism for TMCO1
protein. We classified 41 missense variants as pathogenic based on combined
scores of common in silico tools (SIFT, MutationTaster2, Polyphen2). Of these
41 variants, four (p.K211Q, p.K105E, p.S235F, p.K237R) were identified to be
located in PTMs and regulatory protein binding sites; thus they were proposed
to be putative functional variants. Moreover, rs1387528611 (p.Lys128Gln) had
also strong evidence (RegulomeDB score=2b) for its possible regulatory
function. The results of our in silico analyses highlight the functional
importance of the missense <i>TMCO1 </i>
variants that may contribute to the <i>TMCO1 </i>-associated
disease phenotypes and further in vivo evaluation yet to be needed to uncover
their role in human diseases. </span> </p> <p> </p>}, number={3}, publisher={Duzce University}