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== Summary == ... == Mutation dataset == [[Lab Journal - Task 8 (PAH) #Mutation dataset |Lab journal]] <br> {|border="1" cellspacing="0" cellpadding="5" align="center" style="text-align:center" ! colspan="4" style="background:#32CD32;" | SNPs |- ! style="background:#90EE90;" | AA - three letter ! style="background:#90EE90;" | AA - one letter ! style="background:#90EE90;" | Nucleotides |- |Ala259Val || A259V || C776T |- |Arg123Ile || R123I || G368T |- |Gln20Leu || Q20L || A59T |- |Gln172His || Q172H || G516T |- |Gly103Ser || G103S || G307A |- |Ile421Thr || I421T || T1262C |- |Lys341Thr || K341T || A1022C |- |Phe392Ser || F392S || T1175C |- |Pro416Gln || P416Q || C1247A |- |Thr266Ala || T266A || A796C |} ==Analyze SNPs== The complete results of the prediction tools can be found in the [[Lab Journal - Task 8 (PAH) #Analyze SNPs |Lab journal]]. <br> Looking at the substitution matrices you can see that the substitutions analyzed in this task never have the worst values.<br> As 2pah begins at position 118 for amino acids 20 and 103 the substitutions cannot be shown with pymol. ===Mammalian Homologous Sequences=== We used a normal BLAST search on the mammalian database of Uniprot and filter the [http://www.uniprot.org/blast/uniprot/2013062760F4KDGT75 results] per hand for double entries. Altogether we found 22 homologues sequences (<xr id="IDs"/>). <figtable id="IDs"> {| border="1" style="text-align:center;" cellpadding="5" cellspacing="0" align="center" |- ! colspan="8" style="background:#32CD32;" | UniProt-IDs homologue to P00439 |- | [http://www.uniprot.org/uniprot/H2Q6R0 H2Q6R0] || [http://www.uniprot.org/uniprot/G3S964 G3S964] || [http://www.uniprot.org/uniprot/G1R3M2 G1R3M2] || [http://www.uniprot.org/uniprot/G7PJC2 G7PJC2] || [http://www.uniprot.org/uniprot/F7HMW9 F7HMW9] || [http://www.uniprot.org/uniprot/F7I717 F7I717] || [http://www.uniprot.org/uniprot/F7BKF9 F7BKF9] |- |[http://www.uniprot.org/uniprot/F6XY00 <span style="color:green">F6XY00</span>] || [http://www.uniprot.org/uniprot/E2R366 E2R366] || [http://www.uniprot.org/uniprot/G1T8B6 G1T8B6] || [http://www.uniprot.org/uniprot/H2NIF5 H2NIF5] || [http://www.uniprot.org/uniprot/M3YKN3 M3YKN3] || [http://www.uniprot.org/uniprot/M9P0Q7 M9P0Q7] || [http://www.uniprot.org/uniprot/H0WTI6 H0WTI6] |- |[http://www.uniprot.org/uniprot/M3W9R1 M3W9R1] || [http://www.uniprot.org/uniprot/G3TIW0 G3TIW0] || [http://www.uniprot.org/uniprot/G1LIM6 G1LIM6] || [http://www.uniprot.org/uniprot/Q2KIH7 Q2KIH7] || [http://www.uniprot.org/uniprot/G1P4I7 G1P4I7] || [http://www.uniprot.org/uniprot/P16331 P16331] || [http://www.uniprot.org/uniprot/M9P0Y5 M9P0Y5] |} <center><small>'''<caption>''' UniProt IDs of the 22 mammalian homologues sequences of the PAH protein. The only ID that has a sequence that is not 100% identical to P00439 is marked in green.</caption></small></center> </figtable> For the creation of the multiple alignment we used clustalw. Nevertheless, only F6XY00 has a slightly different sequence. Like E2R366 F6XY00 is a homologue sequence of the human PAH in canis familiaris. On the positions of our substitutions the sequences are conserved. ===Ala-259-Val=== <figure id="A259V"> [[File:A259V.png|thumb|right|'''<caption>''' Mutation of alanine to valine at position 259.</caption>]] </figure> {| border="1" |- | rowspan="2"|Properties || alanine is small, non-polar, neutral and hydrophobic |- | valine is aliphatic, small, non-polar, neutral and hydrophobic |- |Structure || HELIX |- |Substitution Matrices || middle ranged value &rarr; neutral substitution |- |PSSM || alanine seems to be highly conserved with a value of 70. Valine has a value of 1. |- |SIFT || TOLERATED with a score of 0.16 |- |PolyPhen2 || probably damaging with a score of 1.000 |- |SNAP || non-neutral, RI = 2 |- |MutationTaster || disease causing |- | colspan="2" |'''&rArr;''' prediction: '''neutral/non-neutral???''' |} <br clear=all> ===Arg-123-Ile=== <figure id="R123I"> [[File:R123I.png|thumb|right|'''<caption>''' Mutation of alanine to valine at position 259.</caption>]] </figure> {| border="1" |- |rowspan="2" | Properties || arginine is positively charged, polar and hydrophilic |- |isoleucine is aliphatic, neutral, non-polar and hydrophobic |- |Substitution Matrices || low value &rarr; bad substitution |- |Structure ||LOOP |- |PSSM || arginine seems to be highly conserved with a value of 49. Isoleucine has a value of 7. |- |SIFT || AFFECT PROTEIN FUNCTION with a score of 0.00 |- |PolyPhen2 || possibly damaging with a score of 0.807 / 0.582 |- |SNAP || neutral, RI = 0 |- |MutationTaster || disease causing |- | colspan="2" | '''&rArr;''' prediction: '''non-neutral''' |} ===Gln-20-Leu=== {| border="1" |- |rowspan="2"|Properties || glutamine is neutral, polar and hydrophilic |- |leucine is aliphatic, neutral, non-polar and hydrophilic |- |Substitution Matrices || low value &rarr; bad substitution |- |Structure || LOOP |- |PSSM || seems to be not conserved as aspartic acid has a higher value than glutamine: 17-14. Leucine has a value of 6. |- |SIFT || TOLERATED with a score of 0.90 |- |PolyPhen2 || benign with a score of 0.000 |- |SNAP || neutral, RI = 0 |- |MutationTaster || disease causing |- |colspan="2" | '''&rArr;''' prediction: '''neutral''' |} ===Gln-172-His=== <figure id="Q172H"> [[File:Q172H.png|thumb|right|'''<caption>''' Mutation of glutamine to histidine at position 172.</caption>]] </figure> {| border="1" |- |rowspan="2"|Properties || glutamine is neutral, polar and hydrophilic |- | histidine is positively charged, polar and hydrophobic |- |Substitution Matrices || middle ranged &rarr; neutral substitution |- |Structure || LOOP |- |PSSM || ... |- |SIFT || AFFECT PROTEIN FUNCTION with a score of 0.03. |- |PolyPhen2 || possibly damaging with a score of 0.705 / benign with a score of 0.170 |- |SNAP || neutral, RI = 4 |- |MutationTaster || disease causing |- | colspan="2"| '''&rArr;''' prediction: '''neutral''' |} ===Gly-103-Ser=== {| border="1" |- |rowspan="2"|Properties || glycine is small, neutral, non-polar and hydrophilic |- | serine is small, neutral, polar and hydrophilic |- |Substitution Matrices || middle ranged value &rarr; neutral substitution |- |Structure || HELIX |- |PSSM || Glycine seems to be completely unconserved as every amino acid has the same value 5. |- |SIFT || TOLERATED with a score of 0.05 |- |PolyPhen2 || benign with a score of 0.003 / 0.006 |- |SNAP || neutral, RI = 6 |- |MutationTaster || disease causing |- |colspan="2"|'''&rArr;''' prediction: '''neutral''' |} ===Ile-421-Thr=== <figure id="I421T"> [[File:I421T.png|thumb|right|'''<caption>''' Mutation of isoleucine to threonine at position 421.</caption>]] </figure> {| border="1" |- |rowspan="2"|Properties || isoleucine is aliphatic, neutral, non-polar and hydrophobic |- |threonine is small, neutral, polar and hydrophobic |- |Substitution Matrices || low value for Blosum62, middle ranged value for PAM1/250 &rarr; bad or neutral substitution |- |Structure || STRAND |- |PSSM || Isoleucine with a value of 32 seems to be not conserved as valine has a value of 41. Threonine has a value of 0. |- |SIFT || AFFECT PROTEIN FUNCTION with a score of 0.00. |- |PolyPhen2 || possibly damaging with a score of 0.667 / probably damaging with a score of 0.913 |- |SNAP || non-neutral, RI = 2 |- |MutationTaster || disease causing |- | colspan="2"|'''&rArr;''' prediction: '''non-neutral''' |} ===Lys-341-Thr=== <figure id="K341T"> [[File:K341T.png|thumb|right|'''<caption>''' Mutation of lysine to threonine at position 341.</caption>]] </figure> {| border="1" |- |rowspan="2"|Properties || lysine is positively charged, polar and hydrophobic |- | threonine is small, neutral, polar and hydrophobic |- |Substitution Matrices || low value for Blosum62, middle ranged value for PAM1/250 &rarr; bad or neutral substitution |- |Structure || STRAND |- |PSSM || Lysine seems to be conserved with a value of 39. Threonine has a value of 1. |- |SIFT || AFFECT PROTEIN FUNCTION with a score of 0.00. |- |PolyPhen2 || probably damaging with a score of 1.000 / 0.996 |- |SNAP || non-neutral, RI = 3 |- |MutationTaster || disease causing |- |colspan="2" |'''&rArr;''' prediction: '''non-neutral''' |} ===Phe-392-Ser=== <figure id="F392S"> [[File:F392S.png|thumb|right|'''<caption>''' Mutation of phenylalanine to serine at position 392.</caption>]] </figure> {| border="1" |- |rowspan="2"|Properties || phenylalanine is aromatic, neutral, non-polar and hydrophobic |- | serine is small, neutral, polar and hydrophilic |- |Substitution Matrices || low value &rarr; bad substitution |- |Structure || HELIX |- |PSSM || Phenylalanine seems to be highly conserved with a value of 49. Serine has a value of 0. |- |SIFT || AFFECT PROTEIN FUNCTION with a score of 0.00. |- |PolyPhen2 || probably damaging with a score of 1.000 |- |SNAP || non-neutral, RI = 1 |- |MutationTaster || disease causing |- |colspan="2"|'''&rArr;''' prediction: '''non-neutral''' |} ===Pro-416-Gln=== <figure id="P416Q"> [[File:P416Q.png|thumb|right|'''<caption>''' Mutation of proline to glutamine at position 416.</caption>]] </figure> {| border="1" |- |rowspan="2"|Properties || proline is small, neutral, non-polar and hydrophilic |- |glutamine is neutral, polar and hydrophilic |- |Substitution Matrices || low value &rarr; bad substitution |- |Structure || LOOP |- |PSSM || Proline seems to be highly conserved with a value of 66. Glutamine has a value of 0. |- |SIFT || AFFECT PROTEIN FUNCTION with a score of 0.00. |- |PolyPhen2 || probably damaging with a score of 0.996 / 0.985 |- |SNAP || non-neutral, RI = 1 |- |MutationTaster || disease causing |- |colspan="2"|'''&rArr;''' prediction: '''non-neutral''' |} ===Thr-266-Ala=== <figure id="T266A"> [[File:Pah_T266A.png|thumb|right|'''<caption>''' Mutation of threonine to alanine at position 266.</caption>]] </figure> {| border="1" |- |rowspan="2"|Properties || threonine is small, neutral, polar and hydrophobic |- |alanine is small, non-polar, neutral and hydrophobic |- |Substitution Matrices || middle ranged value &rarr neutral substitution |- |Structure || HELIX |- |PSSM || Threonine seems to be conserved with a value of 43. Alanine has a value of 29. |- |SIFT || AFFECT PROTEIN FUNCTION with a score of 0.00. |- |PolyPhen2 || probably damaging with a score of 1.000 |- |SNAP || neutral, RI = 2 |- |MutationTaster || disease causing |- |colspan="2"|'''&rArr;''' prediction: '''non-neutral''' |} == Prediction == {|border="1" cellspacing="0" cellpadding="5" align="center" style="text-align:center" ! colspan="3" style="background:#32CD32;" | SNP-Prediction |- ! style="background:#90EE90;" | SNP ! style="background:#90EE90;" | Prediction ! style="background:#90EE90;" | Validation |- |Ala259Val || neutral/non-neutral??? || || HGMD |- |Arg123Ile || non-neutral || ? || dbSNP |- |Gln20Leu || neutral || wrong || HGMD |- |Gln172His || neutral || ? || dbSNP |- |Gly103Ser || neutral || wrong || HGMD |- |Ile421Thr || non-neutral || ? || dbSNP |- |Lys341Thr || non-neutral || correct || HGMD |- |Phe392Ser || non-neutral || ? || dnSNP |- |Pro416Gln || non-neutral || correct || HGMD |- |Thr266Ala || non-neutral || correct || dbSNP |} == References == <references/> [[Category: Phenylketonuria 2013]]

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