Vinca Lab180

Prediction of epigenetic mutations effects in non-conserved regions

Help

The EpiMutNC tool predict the effects of single amino acid substitutions outside conserved functional domains in epigenetic regulators ASXL1, DNMT3A, EZH2 and TET2, classifying the single nucleotide polymorphism as neutral or pathogenic.
  • In the first drop-down box Gene select one of four epigenetic regulators: ASXL1, EZH2, DNMT3A and TET2.
     
  • EpiMutNC tool enables the user to enter the amino acid substitution in any of the three sequence types: Genomic DNA, Coding DNA and Protein sequence. Select the option from the second drop-down box Sequence type that suites you the most.
     
  • There is two options for entering substitution(s). You can input one single substitution in separate fileds, and in that case the output is supplemented with graphical representation of nonconserved and conserved regions of the analyzed protein and the position of the analyzed amino acid substitution, or you can enter a list of substitutions and the output is given in tabular format.

    In case of selected option Single substitution:
     
    • In the input box Position enter the position of the amino acid substitution in the sequence (in the sequence type you selected previously). EpiMutNC tool only predicts functional effects of amino acid substitutions in nonconserved regions of proteins. If the amino acid substitution you entered is positioned elsewhere, it will be noted in the output.
       
    • Enter the one-letter symbol of the residue in the wild type sequence in the Original residue input box.
      IDs of reference sequences for each of the sequence types are given in the Table below:

      GeneGenomic DNA (RefSeq)Coding DNA (RefSeq)Protein (UniProt)
      ASXL1NM_015338NM_015338Q8IXJ9-1
      EZH2NM_001203247NM_001203247Q15910-1
      DNMT3ANM_022552NM_022552Q9Y6K1-1
      TET2NM_001127208NM_001127208Q6N021-1

       
    • Enter the one-letter symbol of the substitution in the Substitution input field.
       
  • If you select option List of substitutions:
     
    • The input box Substitutions should contain list of amino acid substitution to be analyzed. Each substitution must be in different row. The format of the substitution is position:original_residue>substitution. Maximum number of substitutions is 20.
       
  • The result page displays the information about the selected gene and the amplitude cutoff for the ISM criterion used for the prediction of the functional effect of the amino acid substitution. Predictions are based on the amplitude value on the specific frequency in the informational spectrum of each of the epigenetic regulators: ASXL1: F(0.476); EZH2: F(0.411); DNMT3A: F(0.071) and TET2: F(0.491).
     
  • For the case of Single substitution, the ouput produce: entered amino acid substitution, information about the amplitude value and prediction of the functional effect of the amino acid substitution.
     
  • In case of List of substitutions, the ouput is given in table format. The columns in the table are: amino acid substitution, amplitude value, predicted class SNP / MUTATION and the status in case of some error (i.e. amino acid substitution is not in non-conserved region).
     
  • After textual information, there is a tabular representation of the nonconserved and conserved regions of the analyzed protein, and, in case of "Single substitution" input, graphical representationposition of the analyzed amino acid substitution.
     
  • If any of the input information is incorrect or amino acid substitution is not in the nonconserved region of the selected protein, it will be noted in the output.
     
If you want to analyze more substitutions, please contact us at vladaper@vinca.rs.