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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P07101: Variant p.Phe375Leu

Tyrosine 3-monooxygenase
Gene: TH
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Variant information Variant position: help 375 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Phenylalanine (F) to Leucine (L) at position 375 (F375L, p.Phe375Leu). 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: help Change from large size and aromatic (F) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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
Variant description: help In ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 375 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 528 The length of the canonical sequence.
Location on the sequence: help PEPDCCHELLGHVPMLADRT F AQFSQDIGLASLGASDEEIE 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         PEPDCCHELLGHVPMLADRTFAQFSQDIGLASLGASDEEIE

                              PEPDCCHELLGHVPMLADRTFAQFSQDIGLASLGASDEEIE

Mouse                         PEPDCCHELLGHVPMLADRTFAQFSQDIGLASLGASDEEIE

Rat                           PEPDCCHELLGHVPMLADRTFAQFSQDIGLASLGASDEEIE

Bovine                        PEPECCHELLGHVPMLADRTFAQFSQDIGLASLGVSDEEIE

Caenorhabditis elegans        PEPDLIHELLGHVPMFSDPLLAQMSQDIGLMSLGASDEHIE

Drosophila                    PEPDSIHELLGHMPLLADPSFAQFSQEIGLASLGASDEEIE
Sequence annotation in neighborhood: help 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
Binding site 361 – 361
Binding site 366 – 366
Helix 373 – 386



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: FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; 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.