UniProtKB/Swiss-Prot P21964: Variant p.Val158Met

Catechol O-methyltransferase
Gene: COMT
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Variant information Variant position:

158 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 Valine (V) to Methionine (M) at position 158 (V158M, p.Val158Met). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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
Polymorphism:

Two alleles, COMT*1 or COMT*H with Val-158 and COMT*2 or COMT*L with Met-158 are responsible for a three to four-fold difference in enzymatic activity.Low enzyme activity alleles are associated with genetic susceptibility to alcoholism [MIM:103780]. - Additional information on the polymorphism described.
Variant description:

In allele COMT*2; associated with low enzyme activity and thermolability; may increase the tendency to develop high blood pressure and abdominal obesity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs4680 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

TIEINPDCAAITQRMVDFAG V KDKVTLVVGASQDIIPQLKK 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                         TIEINPDCAAITQRMVDFAGVKDKVTLVVGASQDIIPQLKK

Mouse                         TMEINPDYAAITQQMLDFAGLQDKVSILIGASQDLIPQLKK

Rat                           TMEMNPDYAAITQQMLNFAGLQDKVTILNGASQDLIPQLKK

Bovine                        TIEFNPDYAAITQRMVEFAGLQDKVTVVLGASQDIIPQLKK

Horse                         TIEINPDYAAITQRMLDFAGLQDRVTVVLGASQDIIPQLKK

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 – 271	Catechol O-methyltransferase
Topological domain	27 – 271	Extracellular
Binding site	140 – 140
Binding site	141 – 141
Binding site	169 – 169

Literature citations
A genome annotation-driven approach to cloning the human ORFeome.
Collins J.E.; Wright C.L.; Edwards C.A.; Davis M.P.; Grinham J.A.; Cole C.G.; Goward M.E.; Aguado B.; Mallya M.; Mokrab Y.; Huckle E.J.; Beare D.M.; Dunham I.;
Genome Biol. 5:R84.1-R84.11(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANT MET-158; Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS SER-72 AND MET-158; Submission
Mural R.J.; Istrail S.; Sutton G.G.; Florea L.; Halpern A.L.; Mobarry C.M.; Lippert R.; Walenz B.; Shatkay H.; Dew I.; Miller J.R.; Flanigan M.J.; Edwards N.J.; Bolanos R.; Fasulo D.; Halldorsson B.V.; Hannenhalli S.; Turner R.; Yooseph S.; Lu F.; Nusskern D.R.; Shue B.C.; Zheng X.H.; Zhong F.; Delcher A.L.; Huson D.H.; Kravitz S.A.; Mouchard L.; Reinert K.; Remington K.A.; Clark A.G.; Waterman M.S.; Eichler E.E.; Adams M.D.; Hunkapiller M.W.; Myers E.W.; Venter J.C.;
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]; VARIANT MET-158; Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders.
Lachman H.M.; Papolos D.F.; Saito T.; Yu Y.-M.; Szumlanski C.L.; Weinshilboum R.M.;
Pharmacogenetics 6:243-250(1996)
Cited for: VARIANT COMT*2 MET-158; Catechol-O-methyltransferase (COMT)-mediated metabolism of catechol estrogens: comparison of wild-type and variant COMT isoforms.
Dawling S.; Roodi N.; Mernaugh R.L.; Wang X.; Parl F.F.;
Cancer Res. 61:6716-6722(2001)
Cited for: CHARACTERIZATION OF VARIANT COMT*2 MET-158; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; SUBCELLULAR LOCATION; The V108M mutation decreases the structural stability of catechol O-methyltransferase.
Rutherford K.; Alphandery E.; McMillan A.; Daggett V.; Parson W.W.;
Biochim. Biophys. Acta 1784:1098-1105(2008)
Cited for: CHARACTERIZATION OF VARIANT COMT*2 MET-158; Catechol O-methyltransferase val158-met polymorphism is associated with abdominal obesity and blood pressure in men.
Annerbrink K.; Westberg L.; Nilsson S.; Rosmond R.; Holm G.; Eriksson E.;
Metabolism 57:708-711(2008)
Cited for: VARIANT COMT*2 MET-158;

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.