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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00439: Variant p.Glu280Lys

Phenylalanine-4-hydroxylase
Gene: PAH
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Variant information Variant position: help 280 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 Glutamate (E) to Lysine (K) at position 280 (E280K, p.Glu280Lys). 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 medium size and acidic (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 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 1,2,4,16,38; partial residual activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 280 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 FRVFHCTQYIRHGSKPMYTP E PDICHELLGHVPLFSDRSFA 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                         FRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFA

Mouse                         FRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFA

Rat                           FRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFA

Bovine                        FRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFA

Caenorhabditis elegans        FRVFHSTQYIRHHSAPKYTPEPDICHELLGHVPLFADVEFA

Drosophila                    FRVFHSTQYIRHPSKPMYTPEPDVCHELMGHVPLFADPAFA

Slime mold                    FRVFHATQYIRHPSVPLYTPEPDCCHELLGHVPLLADPDFA
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
Molecular genetics of phenylketonuria in Mediterranean countries: a mutation associated with partial phenylalanine hydroxylase deficiency.
Lyonnet S.; Caillaud C.; Rey F.; Berthelon M.; Frezal J.; Rey J.; Munnich A.;
Am. J. Hum. Genet. 44:511-517(1989)
Cited for: VARIANT PAH DEFICIENCY LYS-280; 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 PAH DEFICIENCY 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 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; 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.