UniProtKB/Swiss-Prot Q8IWU9: Variant p.Arg441His

Tryptophan 5-hydroxylase 2
Gene: TPH2
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Variant information Variant position:

441 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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:

From Arginine (R) to Histidine (H) at position 441 (R441H, p.Arg441His). 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
Variant description:

Linked with susceptibility to major depressive disorder; may be due to a rare RNA editing event; 80% loss of function; decreases solubility; decreases thermal stability; reduces catalytic activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs120074175 [ dbSNP | Ensembl ]

Sequence information Variant position:

441 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

490 The length of the canonical sequence.
Location on the sequence:

VSESFEEAKEKMRDFAKSIT R PFSVYFNPYTQSIEILKDTR 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                         VSESFEEAKEKMRDFAKSITRPFSVYFNPYTQSIEILKDTR

Rhesus macaque                VSESFEEAKEKMRDFAKSITRPFSVYFNPYTQSIEILKDTR

Mouse                         VSDSFEEAKEKMRDFAKSITRPFSVYFNPYTQSIEILKDTR

Rat                           VSESFEEAKEKMRDFAKSITRPFSVYFNPYTQSIEILKDTR

Horse                         VSESFEEAKEKMREFAKSITRPFSVHFNPYTQSVEVLKDSR

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.

Type	Positions	Description
Chain	1 – 490	Tryptophan 5-hydroxylase 2

Literature citations
Brain-specific tryptophan hydroxylase 2 (TPH2): a functional Pro206Ser substitution and variation in the 5'-region are associated with bipolar affective disorder.
Cichon S.; Winge I.; Mattheisen M.; Georgi A.; Karpushova A.; Freudenberg J.; Freudenberg-Hua Y.; Babadjanova G.; Van Den Bogaert A.; Abramova L.I.; Kapiletti S.; Knappskog P.M.; McKinney J.; Maier W.; Jamra R.A.; Schulze T.G.; Schumacher J.; Propping P.; Rietschel M.; Haavik J.; Noethen M.M.;
Hum. Mol. Genet. 17:87-97(2008)
Cited for: BIOPHYSICOCHEMICAL PROPERTIES; VARIANT SER-206; CHARACTERIZATION OF VARIANTS SER-206 AND HIS-441; Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression.
Zhang X.; Gainetdinov R.R.; Beaulieu J.-M.; Sotnikova T.D.; Burch L.H.; Williams R.B.; Schwartz D.A.; Krishnan K.R.R.; Caron M.G.;
Neuron 45:11-16(2005)
Cited for: INVOLVEMENT IN MDD; VARIANT HIS-441; CHARACTERIZATION OF VARIANT HIS-441; Functional properties of missense variants of human tryptophan hydroxylase 2.
McKinney J.A.; Turel B.; Winge I.; Knappskog P.M.; Haavik J.;
Hum. Mutat. 30:787-794(2009)
Cited for: CHARACTERIZATION OF VARIANTS VAL-36; PRO-36; TYR-41; CYS-55; SER-206; TRP-303; VAL-328; HIS-441 AND GLU-479;

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.