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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00439: Variant p.Ala300Ser

Phenylalanine-4-hydroxylase
Gene: PAH
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Variant information Variant position: help 300 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 Alanine (A) to Serine (S) at position 300 (A300S, p.Ala300Ser). 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 small size and hydrophobic (A) to small size and polar (S) 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 PKU and HPA; haplotype 1; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 300 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 EPDICHELLGHVPLFSDRSF A QFSQEIGLASLGAPDEYIEK 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                         EPDICHELLGHVPLFSDRSFAQFSQEIGLASLGAPDEYIEK

Mouse                         EPDICHELLGHVPLFSDRSFAQFSQEIGLASLGAPDEYIEK

Rat                           EPDICHELLGHVPLFSDRSFAQFSQEIGLASLGAPDEYIEK

Bovine                        EPDICHELLGHVPLFSDRSFAQFSQEIGLASLGAPDEYIEK

Caenorhabditis elegans        EPDICHELLGHVPLFADVEFAQFSQEIGLASLGAPDDVIEK

Drosophila                    EPDVCHELMGHVPLFADPAFAQFSQEIGLASLGAPDDYIEK

Slime mold                    EPDCCHELLGHVPLLADPDFADFSQEIGLASIGASDEDIQL

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.
Helix 297 – 310



Literature citations
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; Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian patients with phenylketonuria.
Acosta A.X.; Silva W.A. Jr.; Carvalho T.M.; Gomes M.; Zago M.A.;
Hum. Mutat. 17:122-130(2001)
Cited for: VARIANTS PKU VAL-145; LEU-176; ALA-205; SER-240; CYS-241; LYS-270; GLU-274; SER-300; PRO-311; THR-318; VAL-348; GLY-357 AND GLY-390; 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; Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability.
Gersting S.W.; Kemter K.F.; Staudigl M.; Messing D.D.; Danecka M.K.; Lagler F.B.; Sommerhoff C.P.; Roscher A.A.; Muntau A.C.;
Am. J. Hum. Genet. 83:5-17(2008)
Cited for: CHARACTERIZATION OF VARIANTS PKU LEU-55; SER-65; GLN-170; LEU-275; SER-300; TYR-310; SER-314; TRP-408; CYS-414 AND HIS-417; 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 HPA PHE-39 DEL; LEU-121; TYR-196; TYR-201; ILE-230; SER-300; VAL-306; MET-380; GLY-390 AND VAL-403; VARIANTS PKU VAL-65; TRP-252; GLN-261 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 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.