Rs121907982

General Information

SNP-id	rs121907982
Codon	436
Mutation Codon	Ile -> Val
Mutation Triplt	ATA -> GTA

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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.

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.

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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 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
Amino acid Isoleucine	Amino acid Valin	Picture which visualize the mutation

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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)

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PSSM analysis

	self-information	expected self-information
Ile	-4	1
Val	-3	1

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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.

Mutation in the multiple alignment

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Secondary Structure Mutation Analysis

JPred:
...HHHHHHHHCCCCEEECCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCEEEE...
PsiPred:
...HHHHHHHHCCCEEEECCCCCCCCCCCCCCCCCCCCCCCCCCCCCHHHHCCCCCE...

Comparison with the real structure:

Mutation at position 436

Mutation at position 436 - detailed view

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SNAP Prediction

Substitution	Prediction	Reliability Index	Expected Accuracy
V	Neutral	0	53%

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 w c 436I 1.00 f Y H M p I V g L n T Q D R A S E K

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PolyPhen2 Prediction

HumDiv prediction

HumVar prediction