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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00439: Variant p.Arg252Trp

Phenylalanine-4-hydroxylase
Gene: PAH
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Variant information Variant position: help 252 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 Arginine (R) to Tryptophan (W) at position 252 (R252W, p.Arg252Trp). 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 Change from large size and basic (R) to large size and aromatic (W) 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 PAH deficiency; severe; haplotypes 1,6,7,8,42, 69; complete loss of activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 252 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 QFLQTCTGFRLRPVAGLLSS R DFLGGLAFRVFHCTQYIRHG 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                         QFLQTCTGFRLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHG

Mouse                         QFLQTCTGFRLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHG

Rat                           QFLQTCTGFRLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHG

Bovine                        QFLQSCTGFRLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHG

Caenorhabditis elegans        DFLKDCTGYTIRPVAGLLSSRDFLAGLAFRVFHSTQYIRHH

Drosophila                    NFLRDCTGFTLRPVAGLLSSRDFLAGLAFRVFHSTQYIRHP

Slime mold                    NFLQECTGWRIRPVQGLLSARDFLNGLAFRVFHATQYIRHP
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
Helix 251 – 259



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 PAH DEFICIENCY TRP-252 AND LEU-281; 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 PAH DEFICIENCY; VARIANTS PAH DEFICIENCY 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 PAH DEFICIENCY LEU-20; LEU-39; PRO-41; SER-48; LEU-55; THR-65; SER-68; TYR-84; ASP-104; CYS-110; 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; A phenylalanine hydroxylase amino acid polymorphism with implications for molecular diagnostics.
Gjetting T.; Romstad A.; Haavik J.; Knappskog P.M.; Acosta A.X.; Silva W.A. Jr.; Zago M.A.; Guldberg P.; Guettler F.;
Mol. Genet. Metab. 73:280-284(2001)
Cited for: VARIANTS PAH DEFICIENCY TRP-252 AND THR-318; VARIANT GLU-274; Mutation analysis in Hyperphenylalaninemia patients from South Italy.
Trunzo R.; Santacroce R.; D'Andrea G.; Longo V.; De Girolamo G.; Dimatteo C.; Leccese A.; Lillo V.; Papadia F.; Margaglione M.;
Clin. Biochem. 46:1896-1898(2013)
Cited for: VARIANTS PAH DEFICIENCY PHE-39 DEL; VAL-65; LEU-121; TYR-196; TYR-201; ILE-230; TRP-252; GLN-261; SER-300; VAL-306; MET-380; GLY-390; VAL-403 AND TRP-408; 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 PAH DEFICIENCY 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.