Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00439: Variant p.Pro281Leu

Phenylalanine-4-hydroxylase
Gene: PAH
Feedback?
Variant information Variant position: help 281 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change: help From Proline (P) to Leucine (L) at position 281 (P281L, p.Pro281Leu). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description: help In PKU; haplotypes 1,4. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 281 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 452 The length of the canonical sequence.
Location on the sequence: help RVFHCTQYIRHGSKPMYTPE P DICHELLGHVPLFSDRSFAQ The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         RVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFAQ

Mouse                         RVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFAQ

Rat                           RVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFAQ

Bovine                        RVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFAQ

Caenorhabditis elegans        RVFHSTQYIRHHSAPKYTPEPDICHELLGHVPLFADVEFAQ

Drosophila                    RVFHSTQYIRHPSKPMYTPEPDVCHELMGHVPLFADPAFAQ

Slime mold                    RVFHATQYIRHPSVPLYTPEPDCCHELLGHVPLLADPDFAD

Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 452 Phenylalanine-4-hydroxylase
Binding site 285 – 285
Binding site 290 – 290
Mutagenesis 283 – 283 I -> C. Loss of positive cooperativity and reduction of fold-activation by L-Phe preincubation.



Literature citations
Phenylketonuria missense mutations in the Mediterranean.
Okano Y.; Wang T.; Eisensmith R.C.; Longhi R.; Riva E.; Giovannini M.; Cerone R.; Romano C.; Woo S.L.C.;
Genomics 9:96-103(1991)
Cited for: VARIANTS PKU TRP-252 AND LEU-281; Phenylalanine hydroxylase gene: novel missense mutation in exon 7 causing severe phenylketonuria.
Dworniczak B.; Grudda K.; Stumper J.; Bartholome K.; Aulehla-Scholz C.; Horst J.;
Genomics 9:193-199(1991)
Cited for: VARIANT PKU LEU-281; Phenylalanine hydroxylase deficiency in a population in Germany: mutational profile and nine novel mutations.
Guldberg P.; Mallmann R.; Henriksen K.F.; Guettler F.;
Hum. Mutat. 8:276-279(1996)
Cited for: VARIANTS PKU LEU-40; SER-46; SER-48; 63-THR-HIS-64 DELINS PRO-ASN; THR-65; SER-68; CYS-241; ALA-245; GLN-261; LYS-280; LEU-281; CYS-299; GLY-390; HIS-394; VAL-403; TRP-408 AND CYS-414; Prediction of multiple hypermutable codons in the human PAH gene: codon 280 contains recurrent mutations in Quebec and other populations.
Byck S.; Tyfield L.; Carter K.; Scriver C.R.;
Hum. Mutat. 9:316-321(1997)
Cited for: VARIANTS PKU; VARIANTS PKU GLN-158; TRP-158; LEU-176; PRO-176; ILE-230; CYS-241; HIS-241; LEU-241; GLN-243; GLN-252; GLY-252; TRP-252; GLN-261; PRO-261; LYS-280; LEU-281; CYS-297; HIS-297; THR-322; MET-380; LEU-388; MET-388; GLN-408; TRP-408; PRO-413; SER-413 AND ASN-415; Phenylketonuria and hyperphenylalaninemia in eastern Germany: a characteristic molecular profile and 15 novel mutations.
Hennermann J.B.; Vetter B.; Wolf C.; Windt E.; Buehrdel P.; Seidel J.; Moench E.; Kulozik A.E.;
Hum. Mutat. 15:254-260(2000)
Cited for: VARIANTS PKU LEU-39; PRO-41; SER-48; LEU-55; THR-65; SER-68; TYR-84; ASP-104; PRO-155; GLN-158; GLN-183; ALA-190; THR-211; ILE-230; PHE-231; GLN-243; ALA-245; TRP-252; GLN-261; LEU-281; CYS-299; SER-300; VAL-306; VAL-309; CYS-325; ASP-330; ARG-344; VAL-344; VAL-348; PRO-349; CYS-386; GLY-390; PRO-395; VAL-403; TRP-408; SER-410 AND CYS-414; VARIANTS HPA LEU-20 AND CYS-110; Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria.
Muntau A.C.; Roschinger W.; Habich M.; Demmelmair H.; Hoffmann B.; Sommerhoff C.P.; Roscher A.A.;
N. Engl. J. Med. 347:2122-2132(2002)
Cited for: VARIANTS HPA LEU-39; LEU-55; VAL-65; MET-177; ALA-245; GLN-261; TYR-310; SER-314; VAL-403; TRP-408; CYS-414 AND ASN-415; VARIANTS PKU SER-48; ASP-61; SER-65; THR-65; VAL-65; GLN-158; GLN-170; GLN-261; LEU-275; LEU-281; SER-300; GLY-390; TRP-408; PRO-413; CYS-414 AND HIS-417; Five novel mutations and two large deletions in a population analysis of the phenylalanine hydroxylase gene.
Groselj U.; Tansek M.Z.; Kovac J.; Hovnik T.; Podkrajsek K.T.; Battelino T.;
Mol. Genet. Metab. 106:142-148(2012)
Cited for: VARIANTS PKU ALA-45; SER-48; PRO-62; SER-157; GLN-158; LEU-177; GLY-178; ALA-190; HIS-226; ALA-245; TRP-252; GLN-261; LYS-280; LEU-281; SER-300; PRO-349; GLY-390; VAL-403; TRP-408 AND ASN-415;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.