| Summary: | Transmembraneand Coiled-Coil Domains 1 (TMCO1) protein is encoded by TMCO1 gene consists of 7 exons. Previous studies have identifiedmultiple TMCO1 variants in patientswith cerebro-facio-thoracic dysplasia (CFTD) and TMCO1 locus was also shown to be associated with primary open angleglaucoma (POAG). However, there are limited number of research exist reportingassociations of the TMCO1 genesequence variants and majority of the findings affirm the pathogenicity of thenonsense and frameshift TMCO1 variantsand their associations with clinical phenotypes. Thus functional properties ofthe single nucleotide variants causing amino acid changes in the TMCO1 are yetto be comprehensively elucidated. In this study, we evaluated the effects ofamino acid substitutions on protein structure, identified their putative rolesin post-translational modifications (PTM) and in regulatory mechanism for TMCO1protein. We classified 41 missense variants as pathogenic based on combinedscores of common in silico tools (SIFT, MutationTaster2, Polyphen2). Of these41 variants, four (p.K211Q, p.K105E, p.S235F, p.K237R) were identified to belocated in PTMs and regulatory protein binding sites; thus they were proposedto be putative functional variants. Moreover, rs1387528611 (p.Lys128Gln) hadalso strong evidence (RegulomeDB score=2b) for its possible regulatoryfunction. The results of our in silico analyses highlight the functionalimportance of the missense TMCO1variants that may contribute to the TMCO1-associateddisease phenotypes and further in vivo evaluation yet to be needed to uncovertheir role in human diseases.
|
|---|