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UniProtKB/Swiss-Prot P07101: Variant p.Thr314Met

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

Variant position:  314
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 Threonine (T) to Methionine (M) at position 314 (T314M, p.Thr314Met).
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 polar (T) to medium size and hydrophobic (M)
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:  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; parkinsonian symptoms in infancy; loss of about 80% of tyrosine hydroxylase activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  314
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:   GYREDNIPQLEDVSRFLKER  T GFQLRPVAGLLSARDFLASL
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                         GYREDNIPQLEDVSRFLKERTGFQLRPVAGLLSARDFLASL

                              GYREDSIPQLEDVSRFLKERTGFQLRPVAGLLSARDFLASL

Mouse                         GYREDSIPQLEDVSHFLKERTGFQLRPVAGLLSARDFLASL

Rat                           GYREDSIPQLEDVSRFLKERTGFQLRPVAGLLSARDFLASL

Bovine                        GYREDRIPQLEDVSRFLKERTGFQLRPAAGLLSARDFLASL

Caenorhabditis elegans        VLTADRIPQIRDVNKFLQKKTGFELRPCSGLLSARDFLASL

Drosophila                    IFVETRLPQLQEMSDFLRKNTGFSLRPAAGLLTARDFLASL

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
Alternative sequence 264 – 357 Missing. In isoform 5 and isoform 6.
Helix 303 – 314


Literature citations

Four novel mutations in the tyrosine hydroxylase gene in patients with infantile parkinsonism.
Swaans R.J.M.; Rondot P.; Renier W.O.; Van Den Heuvel L.P.W.J.; Steenbergen-Spanjers G.C.H.; Wevers R.A.;
Ann. Hum. Genet. 64:25-31(2000)
Cited for: VARIANTS ARSEGS PRO-276; MET-314; HIS-337 AND MET-494;

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.