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UniProtKB/Swiss-Prot P30793: Variant p.Asp115Asn

GTP cyclohydrolase 1
Gene: GCH1
Variant information

Variant position:  115
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 Aspartate (D) to Asparagine (N) at position 115 (D115N, p.Asp115Asn).
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 medium size and acidic (D) to medium size and polar (N)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  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

Involvement in disease:  Dystonia, dopa-responsive (DRD) [MIM:128230]: A form of dystonia that responds to L-DOPA treatment without side effects. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DRD typically presents in childhood with walking problems due to dystonia of the lower limbs and worsening of the dystonia towards the evening. It is characterized by postural and motor disturbances showing marked diurnal fluctuation. Torsion of the trunk is unusual. Symptoms are alleviated after sleep and aggravated by fatigue and exercise. {ECO:0000269|PubMed:10076897, ECO:0000269|PubMed:10208576, ECO:0000269|PubMed:10582612, ECO:0000269|PubMed:10825351, ECO:0000269|PubMed:10987649, ECO:0000269|PubMed:11113234, ECO:0000269|PubMed:12391354, ECO:0000269|PubMed:17101830, ECO:0000269|PubMed:7501255, ECO:0000269|PubMed:7874165, ECO:0000269|PubMed:8852666, ECO:0000269|PubMed:8957022, ECO:0000269|PubMed:9120469, ECO:0000269|PubMed:9328244, ECO:0000269|PubMed:9778264}. 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 DRD.
Any additional useful information about the variant.



Sequence information

Variant position:  115
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  250
The length of the canonical sequence.

Location on the sequence:   PWRAASAMQFFTKGYQETIS  D VLNDAIFDEDHDEMVIVKDI
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                         PWRAASAMQFFTKGYQETI-SDVLNDAIFDEDHDEMVIVKDI

Mouse                         PWRAATAMQYFTKGYQETI-SDVLNDAIFDEDHDEMVIVKD

Rat                           PWRAATAMQFFTKGYQETI-SDVLNDAIFDEDHDEMVIVKD

Chicken                       PWRAATAMQFFTKGYQETI-ADVLNDAIFDEDHDEMVIVKN

Caenorhabditis elegans        PERAAKAMMAFTKGYDDQL-DELLNEAVFDEDHDEMVIVKD

Drosophila                    PERAAKAMLYFTKGYDQSL-EDVLNGAVFDEDHDEMVVVKD

Slime mold                    PLRMSKALLFFTQGYEQSV-DEVIGEAIFNENHHEMVVVRD

Baker's yeast                 PQRYAKAMLYFTKGYQTNIMDDVIKNAVFEEDHDEMVIVRD

Fission yeast                 PERYAKAMLYFTKGYEQNL-TEVINEAVFQEDHEEMVIVRD

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
Chain 1 – 250 GTP cyclohydrolase 1
Turn 113 – 115


Literature citations

GTP cyclohydrolase I mutations in patients with dystonia responsive to anticholinergic drugs.
Jarman P.R.; Bandmann O.; Marsden C.D.; Wood N.W.;
J. Neurol. Neurosurg. Psych. 63:304-308(1997)
Cited for: VARIANTS DRD LEU-23 AND ASN-115;

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.