Home  |  Contact

UniProtKB/Swiss-Prot P09417: Variant p.Gly17Val

Dihydropteridine reductase
Gene: QDPR
Variant information

Variant position:  17
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Glycine (G) to Valine (V) at position 17 (G17V, p.Gly17Val).
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:  Change from glycine (G) to medium size and hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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

Involvement in disease:  Hyperphenylalaninemia, BH4-deficient, C (HPABH4C) [MIM:261630]: Rare autosomal recessive disorder characterized by hyperphenylalaninemia and severe neurologic symptoms (malignant hyperphenylalaninemia) including axial hypotonia and truncal hypertonia, abnormal thermogenesis, and microcephaly. These signs are attributable to depletion of the neurotransmitters dopamine and serotonin, whose syntheses are controlled by tryptophan and tyrosine hydroxylases that use BH-4 as cofactor. Patients do not respond to phenylalanine-restricted diet. HPABH4C is lethal if untreated. {ECO:0000269|PubMed:10408783, ECO:0000269|PubMed:11153907, ECO:0000269|PubMed:2116088, ECO:0000269|PubMed:8326489, ECO:0000269|PubMed:9744478}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HPABH4C; severe.
Any additional useful information about the variant.



Sequence information

Variant position:  17
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  244
The length of the canonical sequence.

Location on the sequence:   MAAAAAAGEARRVLVY  G GRGALGSRCVQAFRARNWWV
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         MAAAAAAGEARRVLVYGGRGALGSRCVQAFRARNWWV

Mouse                         ---MAASGEARRVLVYGGRGALGSRCVQAFRARNWWV

Rat                           ---MAASGEARRVLVYGGRGALGSRCVQAFRARNWWV

Pig                           -MAAAAAGEARRVLVYGGRGALGSRCVQAFRARNWWV

Bovine                        --MAAAAGEARRVLVYGGRGALGSRCVQAFRARNWWV

Slime mold                    --------MSKNILVLGGSGALGAEVVKFFKSKSWNT

Sequence annotation in neighborhood:  
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
Initiator methionine 1 – 1 Removed
Chain 2 – 244 Dihydropteridine reductase
Nucleotide binding 14 – 38 NADP
Modified residue 2 – 2 N-acetylalanine
Turn 17 – 19


Literature citations

A series of mutations in the dihydropteridine reductase gene resulting in either abnormal RNA splicing or DHPR protein defects.
Smooker P.M.; Gough T.J.; Cotton R.G.H.; Alliaudi C.; de Sanctis L.; Dianzani I.;
Hum. Mutat. 13:503-504(1999)
Cited for: VARIANTS HPABH4C PRO-14 AND VAL-17;

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.