Rs121907982
Contents
General Information
| SNP-id | rs121907982 |
| Codon | 436 |
| Mutation Codon | Ile -> Val |
| Mutation Triplt | ATA -> GTA |
Pysicochemical Properities
First of all, we explored the amino acid properties and compared them for the original and the mutated amino acid. Therefore we created the possible effect that the mutation could have on the protein.
| Ile | Val | consequences |
| aliphatic, hydrophobic, neutra | aliphatic, hydrophobic, neutral | In this case, the pysicochemical properties are equal. Furthermore, they almost agree in their size. Therefore, we suggest, that there is no big effect on the 3D structure of the protein and therefore, also no big effect on the protein function. |
Visualisation of the Mutation
In the next step, we created the visualization of the muation with PyMol. Therefore we created a picture for the original amino acid, for the new mutated amino acid and finally for both together in one picture whereas the mutation is white colored. The following pictures display the mutation from Isoleucine to Valine. Isoleucine is longer than Valine and one part spreads in the other direction than this of Valine. Valine is small and forks at its end. All in all, the differencesof both amino acids is not so drastical and therefore the protein will probably not have a strutural and functional change.
| picture original aa | picture mutated aa | combined picture |
Subsitution Matrices Values
Afterwards, we looked at the values of the substitution matrices PAM1, PAM250 and BLOSSUM62. Therefore we looked detailed at the three values: the value for accoding amino acid substitution, the most frequent value for the substitution of the examined amino acid and the rarest substitution.
In this case, the substitution of Isoleucine to Valine has very high values that agree with the most frequent value for all three substitution matrices. Therefore, according to all matrices a mutation at this position will probably not cause structural changes which can affect functional changes.
| PAM 1 | Pam 250 | BLOSOUM 62 | ||||||
| value aa | most frequent substitution | rarest substitution | value aa | most frequent substitution | rarest substitution | value aa | most frequent substitution | rarest substitution |
| 33 | 33 (Val) | 0 (Gly, Pro, Trp) | 9 | 9 (Val) | 1 (Trp) | 3 | 3 (Val) | -4 (Gly) |
PSSM analysis
| self-information | expected self-information | |
| Ile | -4 | 1 |
| Val | -3 | 1 |
Conservation Analysis with Multiple Alignments
As a next step we created a multiple alignment which contains the HEXA sequence and 9 other mammalian homologous sequences from uniprot. Afterwards we looked at the position of the different mutations and looked at the conservation level on this position. The regarded mutation is presented by the second colored column. Here we can see, that almost all other mammalians have another amino acid on this position. Therefore, the mutation on this position is not highly conserved and a mutation there will cause probably no huge structural and functional changes for the protein.
Secondary Structure Mutation Analysis
As a next step we compared the different results of the secondary structure prediction tools JPred and PsiPred. Afterwards we can examine in which secondary structure element and where therein the mutation takes place. This can give an overview of how drastical the mutation can be. In this case both tools agree and predict at the position of the mutation a coil. This has a result, that the mutation at this position would not destroy or split a secondary structure element. It will probably only changes the coil between two secondary structure elements, but this can sometimes also cause a change of the the following secondary structure. We think that a drastical change of the protein structure and its function is unlikly because the mutation does not affect a secondary struture element. The change of the coil will probably only take places between two secondary structure elements which will probably not changes the protein.
JPred: ...HHHHHHHHCCCCEEECCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCEEEE... PsiPred: ...HHHHHHHHCCCEEEECCCCCCCCCCCCCCCCCCCCCCCCCCCCCHHHHCCCCCE...
Comparison with the real Structure:
Afterwards we also visualize the position of the muation (red) in the real 3D-structure of PDB and compare it with the predicted secondary structure. The visualisation can therefore like above the predicted secondary structure display if the mutation is in a secondary structure element or in some other regions.
Here in this case the mutationposition almost agree with the position of the predicted secondary structure and is within a coil. Like explained above this means a mutation will probably not destroy a secondary structure element which affects no drastical structural change. Otherwise it can cause a change of the position of the two nearest secondary structure element which can has a functional loose as a consequence. We think that a structural change is unlikely, because it is not within a secondary structure element and will therefore not cause extrem changes of the protein.
SNAP Prediction
Next, we looked at the result of the SNAP prediction. For this prediction we took the amino acid of the certain position and checked every possible amino acid mutation. Afterwards we extract the result for Aspartic acid which is the real mutation in this case. SNAP has a result that the exhange from Asparagine to Aspartic acid at this position is neutral with an average accuracy of only 53%. The low accuracy is critical for this prediction, but we suppose that it is right and the mutation at this position is neutral which means it likely causes no structural and functional changes of the protein.
| Substitution | Prediction | Reliability Index | Expected Accuracy |
| V | Neutral | 0 | 53% |
A detailed list of all possible substitutions can be found here]
SIFT Prediction
SIFT Matrix:
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.
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SIFT Table
Threshold for intolerance is 0.05.
Amino acid color code: nonpolar, uncharged polar, basic, acidic.
Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.
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