Rs4777505

General Information

SNP-ID	Rs4777505
Codon Number	29
Mutation Codon	Asn -> Ser
Mutation Triplet	AAC -> AGC

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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.

Asn	Ser	consequences
polar, small, hydrophilic, negatively charged	polar, tiny, hydrophilic, neutral	Both amino acids are polar and hydrophilic. Ser is tiny, Asn therefore is a small amino acid. The biggest difference between these two amino acid is, that Asn is negatively charged and Ser is neutral. But this is not that big difference and therefore we suggest, that this mutation do not delete the structure and 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 original amino acid Asparagine has a much smaller chain than Serine. Contrary Serine is longer and comes to a fork at the end of its rest. Furthermore, it is also orientated in a different direction. Otherwise comparing to other mutations this one is not extremly. Therefore, this exchange will probably not cause huge effects on the protein structure and function.

picture original aa	picture mutated aa	combined picture
Amino acid Asparagine	Amino acid Serine	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 Asparagine to Serine has very high values that is nearer to the values for the most frequent subsitution for PAM1. Contrary for PAM250 the value for the amino acid subsitution Leucine to Arginine is average. This means the most frequent subsitution value is almost as far as the rarerest subsitution from the the underlying value. The difference between the two PAMs can be ascribed to the different preparations of these two kind of substitutions matrices. For the PAM1-matrice the substitution rate is 1% which means the prabability that one amino acid changes is 1% and that there is 99% similarity. Contrary, PAM250 means that 250 mutations have been fixed per 100 residues which has as result only similarity about 20%. A possible reason that PAM250 has a better value for the amino acid substitution is that the similarity is low and the amino acids are probably dissimilar. Finally, both PAM-matrices show that this mutation is very common. BLOSOUM62 has a very bad value which corresponds to the most frequent substitution. BLOSSUM62 is based on protein families which means that this substitution is very common in some protein families. All in all, all three substitution matrices point out that this specific substitution from Asparagine to Serine is very frequent. A possible consequence can therefor be that this mutation has no drastical effects on the protein.

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
20	36 (Asp)	0 (Cys, Met)	5	7 (Asp)	2 (Cys, Leu, Phe, Trp)	1	1 (Asp, His, Ser)	-4 (Trp)

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PSSM analysis

	self-information	expexted self-information
Asn	1	5
Ser	3	24

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Conservation Analysis with Multiple Alignments

Mutation in the multiple alignment

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Secondary Structure Mutation Analysis

JPred:
CCHHHHHHHHHHHHHCCCCCCCEEEEEEEEEECCCEEEEECCCEEEEECCCCCCC...
PsiPred:
CHHHHHHHHHHHHHHHCCCCCCCCCCCCEEEECCCEEEEECCCEEEEECCCCCCC...

Comparison with the real structure:

Mutation at position 29

Mutation at position 29 - detailed view

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SNAP Prediction

Substitution	Prediction	Reliability Index	Expected Accuracy
S	Neutral	8	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 w 29N 0.78 c f M H i Y p V g L R N d Q T A S K E

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PolyPhen2 Prediction

HumDiv prediction

HumVar prediction