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UniProtKB/Swiss-Prot P07101: Variant p.Arg233His

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

Variant position:  233
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 Arginine (R) to Histidine (H) at position 233 (R233H, p.Arg233His).
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 large size and basic (R) to medium size and polar (H)
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; shifted substrate specificity from tyrosine to phenylalanine and Dopa.
Any additional useful information about the variant.

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



Sequence information

Variant position:  233
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:   KFDPDLDLDHPGFSDQVYRQ  R RKLIAEIAFQYRHGDPIPRV
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                         KFDPDLDLDHPGFSDQVYRQRRKLIAEIAFQYRHGDPIPRV

                              KFDPDLDLDHPGFSDQVYRQRRKLIAEIAFQYKHGDPIPRV

Mouse                         KFDPDLDLDHPGFSDQAYRQRRKLIAEIAFQYKQGEPIPHV

Rat                           KFDPDLDLDHPGFSDQVYRQRRKLIAEIAFQYKHGEPIPHV

Bovine                        KFDPDLDLDHPGFSDQAYRQRRKLIAEIAFQYKQGDPIPHV

Caenorhabditis elegans        KYEPTTDPRHPGHGDVAYIARRKFLNDQALEFKFGDEIGYV

Drosophila                    KYEPDLDMNHPGFADKVYRQRRKEIAEIAFAYKYGDPIPFI

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
Helix 228 – 243


Literature citations

A common point mutation in the tyrosine hydroxylase gene in autosomal recessive L-DOPA-responsive dystonia in the Dutch population.
van den Heuvel L.P.W.J.; Luiten B.; Smeitink J.A.M.; de Rijk-van Andel J.F.; Hyland K.; Steenbergen-Spanjers G.C.H.; Janssen R.J.T.; Wevers R.A.;
Hum. Genet. 102:644-646(1998)
Cited for: VARIANT ARSEGS HIS-233;

Molecular analyses of GCH-1, TH and parkin genes in Chinese dopa-responsive dystonia families.
Wu Z.Y.; Lin Y.; Chen W.J.; Zhao G.X.; Xie H.; Murong S.X.; Wang N.;
Clin. Genet. 74:513-521(2008)
Cited for: VARIANTS ARSEGS HIS-233 AND SER-247;

Tyrosine hydroxylase deficiency in Taiwanese infants.
Chi C.S.; Lee H.F.; Tsai C.R.;
Pediatr. Neurol. 46:77-82(2012)
Cited for: VARIANTS ARSEGS HIS-233; SER-315 AND THR-382;

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.