Home  |  Contact

UniProtKB/Swiss-Prot P07101: Variant p.Ser467Gly

Tyrosine 3-monooxygenase
Gene: TH
Chromosomal location: 11p15.5
Variant information

Variant position:  467
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 Serine (S) to Glycine (G) at position 467 (S467G, p.Ser467Gly).
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 small size and polar (S) to glycine (G)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Segawa syndrome autosomal recessive (ARSEGS) [MIM:605407]: A form of DOPA-responsive dystonia presenting in infancy or early childhood. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Some cases present with parkinsonian symptoms in infancy. Unlike all other forms of dystonia, it is an eminently treatable condition, due to a favorable response to L-DOPA. {ECO:0000269|PubMed:10585338, ECO:0000269|PubMed:11196107, ECO:0000269|PubMed:11246459, ECO:0000269|PubMed:15505183, ECO:0000269|PubMed:15747353, ECO:0000269|PubMed:16049992, ECO:0000269|PubMed:17696123, ECO:0000269|PubMed:18058633, ECO:0000269|PubMed:18554280, ECO:0000269|PubMed:19491146, ECO:0000269|PubMed:20056467, ECO:0000269|PubMed:20430833, ECO:0000269|PubMed:21940685, ECO:0000269|PubMed:22264700, ECO:0000269|PubMed:22815559, ECO:0000269|PubMed:23762320, ECO:0000269|PubMed:23939262, ECO:0000269|PubMed:24753243, ECO:0000269|PubMed:7814018, ECO:0000269|PubMed:8528210, ECO:0000269|PubMed:8817341, ECO:0000269|PubMed:9613851, ECO:0000269|PubMed:9703425}. 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 ARSEGS; loss of over 80% of tyrosine hydroxylase activity.
Any additional useful information about the variant.



Sequence information

Variant position:  467
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  528
The length of the canonical sequence.

Location on the sequence:   AAAVQPYQDQTYQSVYFVSE  S FSDAKDKLRSYASRIQRPFS
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                         AAAVQPYQDQTYQSVYFVSESFSDAKDKLRSYASRIQRPFS

                              AAAVQPYQDQTYQSVYFVSESFSDAKDKLRNYASRIQRPFS

Mouse                         TAAVQPYQDQTYQPVYFVSESFSDAKDKLRNYASRIQRPFS

Rat                           TAAVQPYQDQTYQPVYFVSESFNDAKDKLRNYASRIQRPFS

Bovine                        AAAVQPYQDQTYQPVYFVSESFSDAKDKLRSYASRIQRPFS

Caenorhabditis elegans        VTAVQKYEDDDYQPLYFVADSIHDALAKLRKYASSMDRPFS

Drosophila                    STAVQPYQDQEYQPIYYVAESFEDAKDKFRRWVSTMSRPFE

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 – 528 Tyrosine 3-monooxygenase


Literature citations

Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia.
Clot F.; Grabli D.; Cazeneuve C.; Roze E.; Castelnau P.; Chabrol B.; Landrieu P.; Nguyen K.; Ponsot G.; Abada M.; Doummar D.; Damier P.; Gil R.; Thobois S.; Ward A.J.; Hutchinson M.; Toutain A.; Picard F.; Camuzat A.; Fedirko E.; San C.; Bouteiller D.; LeGuern E.; Durr A.; Vidailhet M.; Brice A.;
Brain 132:1753-1763(2009)
Cited for: VARIANTS ARSEGS ALA-301; PRO-319; LEU-375; ARG-414 AND GLY-467;

Functional studies of tyrosine hydroxylase missense variants reveal distinct patterns of molecular defects in Dopa-responsive dystonia.
Fossbakk A.; Kleppe R.; Knappskog P.M.; Martinez A.; Haavik J.;
Hum. Mutat. 35:880-890(2014)
Cited for: CHARACTERIZATION OF VARIANTS ARSEGS TYR-207; GLY-227; HIS-233; PRO-236; THR-241; TYR-246; SER-247; GLY-259; PRO-276; ALA-301; SER-309; MET-314; PRO-319; TRP-328; HIS-337; PHE-359; LEU-375; VAL-376; MET-387; THR-394; MET-399; LYS-412; ARG-414; PRO-441; GLY-467; LEU-492; MET-494; GLY-498 AND GLN-510;

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.