Rs121907968

General Information

SNP-id	rs121907968
Codon	485
Mutation Codon	Trp -> Arg
Mutation Triplet	gTGG -> CGG

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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.

Trp	Arg	consequences
aromatic, polar, hydrophobic, neutral	positive charged, polar, hydrophilic	Trp is very big, because of two aromatic rings in its structure. Furthermore, it is hydrophobic, whereas, Arg is a hydrophilic amino acid. Therefore, the changes in the 3D structure might be extreme and delete the function of the protein.

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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 Arginine looks very different to Tryptophan. Tryptophan has two huge aromatical rings. Contrary, Aspartate is also a long amino acid and forks at the end of the rest. Furthermore, Arginige is also orientated in a completly different direction. Because of the aromatical rings the differences between these two amino acids is realy huge. Therefore, the amino acids will probably cause drastical effects on protein structure and function.

picture original aa	picture mutated aa	combined picture
Amino acid Tryptophan	Amino acid Arginine	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	2 (Arg)	0 (all, except Arg, Phe, Ser, Tyr)	2	2 (Arg)	0 (all, except Arg, His, Leu, Phe, Ser, Tyr)	-3	2 (Tyr)	-4 (Asn, Asp, Pro)

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PSSM analysis

	self-information	expected self-information
Trp	13	99
Arg	-6	0

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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 all other mammalians have also on this position the amino acid Tryptophan. Therefore, the mutation on this position is highly conserved and a mutation there will cause probably huge structural and functional changes for the protein.

Mutation in the multiple alignment

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Secondary Structure Mutation Analysis

JPred:
...HHHHCCCCCCCCHHHHHHHHHHHHHHHHHCCCCCCCCCCCCCCHHHCCC...
PsiPred:
...HHHCCCCCCCCCHHHHHHHHHHHHHHHHHCCCCCCCCCCCCCCCCCCCC...

Comparison with the real structure:

Mutation at position 485

Mutation at position 485 - detailed view

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SNAP Prediction

Substitution	Prediction	Reliability Index	Expected Accuracy
R	Non-neutral	7	96%

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 y v t s r q p n m l k i h g f e d c a 485W 0.97 W

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PolyPhen2 Prediction

HumDiv prediction

HumVar prediction