Rs61731240

General Information

SNP-id	rs61731240
Codon	179
Mutation Codon	His -> Asp
Mutation Triplet	CAT -> GAT

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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.

His	Asp	consequences
aromatic, positive charged, polar, hydrophilic	negative charged, small, polar, hydrophilic	On the one side, both amino acids are polar, but on the other side, His is positively charged, while Asp is negatively charged, which is an essential difference between these both amino acids. Therefore it is very likely, that this change causes big changes in the structure of the protein and the protein therefore will probably not work any longer. Furthermore, the structure of the two amino acids is very different, because of the aromatic ring of the His.

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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 that the mutated amino acid Histidine looks very different to Aspartate. Histidine has an aromatical ring. Contrary, Aspartate is smaller and forks at the end of the rest. Furthermore, it is also orientated in a completly different direction. This shows that the amino acids have huge structural differences which will probably cause drastical effects on protein structure and function.

picture original aa	picture mutated aa	combined picture
Amino acid Histidine	Amino acid Aspartate	Picture which visualize the mutation

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Subsitution Matrices Values

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
3	20 (Gln)	0 (Ile, Met)	4	7 (Gln)	2 (Ala, Cys, Gly, Ile, Leu, Met, Phe, Thr, Trp, Val)	-1	2 (Tyr)	-3 (Cys, Ile, Leu, Val)

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PSSM analysis

	self-information	expected self-information
His	9	65
Asp	-3	0

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Conservation analysis with Multiple Alignments

Mutation in the multiple alignment

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Secondary Structure Mutation Analysis

JPred:
...EEEECCCCCEEEEEECCCCCCCHHHHHHHHHHHHHHCCCEEEEEEECCCCCCCCC...
PsiPred:
...EEECCCCCCCCCCCCCCCCCCCHHHHHHHHHHHHHCCCCEEEEEECCCCCCCEEC...

Comparison with the real structure:

Mutation at position 179

Mutation at position 179 - detailed view

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SNAP Prediction

Substitution	Prediction	Reliability Index	Expected Accuracy
D	Non-neutral	6	93%

A detailed list of all possible substitutions can be found [here]

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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.

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.

Predict Not Tolerated Position Seq Rep Predict Tolerated m w f c i y v l t a s p e r n d k g Q 179H 0.99 H

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Polyphen2 Prediction

HumDiv prediction

HumVar prediction