Rs1054374

General Information

SNP-id	rs1054374
Codon	293
Mutation Codon	Ser -> Ile
Mutation Triplet	AGT -> ATT

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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.

Ser	Ile	consequences
polar, tiny, hydrophilic, neutral	aliphatic, hydrophobic, neutra	Ile is much bigger than Ser and also is branched, because it is an aliphatic amino acid. Therefore the structure of both amino acids is really different and Ile is to big for the position where Ser was. Therefore, there has to be a big change in the 3D structure of the protein and the protein probably will loose its 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 that the original amino acid Serine looks different to Isoleucine. Serine is very small whereas Isoleucine is bigger and has two spreadin chains. The first part of the rest agrees in both amino acids. In this case the difference is not so heavy, but can also cause some structural changes which can have affects on the protein function. All in all, the mutation will probably have no structural or functional changes.

picture original aa	picture mutated aa	combined picture
Amino acid Serine	Amino acid Isoleucine	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
2	38 (Thr)	1 (Leu)	5	9 (Ala, Gly, Pro, Thr)	3 (Phe)	-2	1 (Ala, Asn, Thr)	-3 (Trp)

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PSSM analysis

	self-information	expected self-information
Ser	1	10
Ile	1	7

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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 colored column. Here we can see, that the many other mammalians have on this position another amino acid. Only four other mammalian agrees and have at this position a Serine. Therefore, the mutation on this position is not highly conserved and a mutation there will cause probably no structural and functional changes for the protein.

Mutation in the multiple alignment

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Secondary Structure Mutation Analysis

JPred:
...HHHHHHHHCCCEEEECCCCCHHHHHHHHHCCCCCCCCCCCCCCCCCCCCCCCCCC...
PsiPred:
...HHHHHHHHCCCEEEECCCCCHHHHHHHHCCCCCCCCCCCCCCCCCCCCCCCCCCH...

Comparison with the real structure:

Mutation at position 293

Mutation at position 293 - detailed view

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SNAP Prediction

Substitution	Prediction	Reliability Index	Expected Accuracy
I	Neutral	2	69%

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 g h y d r n f q e k c p 293S 1.00 M l A S V T I

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PolyPhen2 Prediction

HumDiv prediction

HumVar prediction