UniProtKB/Swiss-Prot P78329: Variant p.Val433Met

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 433 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 433 (V433M, p.Val433Met). 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
Variant description: Risk factor for coumarin resistance; increased warfarin maintenance dose in patients on warfarin anti-coagulant therapy due to decreased vitamin K catabolism; decreased phylloquinone omega-hydroxylase activity; decreased production of 20-hydroxyeicosatetraenoic acid (20-HETE). Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs2108622 [ dbSNP | Ensembl ]

Sequence information

Variant position: 433 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 520 The length of the canonical sequence.
Location on the sequence: VIPKGIICLISVFGTHHNPA V WPDPEVYDPFRFDPENIKER 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.
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	5 – 520	Cytochrome P450 4F2
Alternative sequence	340 – 520	Missing. In isoform 2.

Literature citations

Submission
SeattleSNPs variation discovery resource;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS TYR-7; GLY-12; VAL-185; MET-433 AND MET-519; The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1); VARIANTS GLY-12 AND MET-433; Functional polymorphism in human CYP4F2 decreases 20-HETE production.
Stec D.E.; Roman R.J.; Flasch A.; Rieder M.J.;
Physiol. Genomics 30:74-81(2007)
Cited for: FUNCTION; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANT MET-433; The V433M variant of the CYP4F2 is associated with ischemic stroke in male Swedes beyond its effect on blood pressure.
Fava C.; Montagnana M.; Almgren P.; Rosberg L.; Lippi G.; Hedblad B.; Engstrom G.; Berglund G.; Minuz P.; Melander O.;
Hypertension 52:373-380(2008)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT MET-433; CYP4F2 genetic variant alters required warfarin dose.
Caldwell M.D.; Awad T.; Johnson J.A.; Gage B.F.; Falkowski M.; Gardina P.; Hubbard J.; Turpaz Y.; Langaee T.Y.; Eby C.; King C.R.; Brower A.; Schmelzer J.R.; Glurich I.; Vidaillet H.J.; Yale S.H.; Qi Zhang K.; Berg R.L.; Burmester J.K.;
Blood 111:4106-4112(2008)
Cited for: INVOLVEMENT IN CMRES; CHARACTERIZATION OF VARIANT MET-433; Pharmacogenetic relevance of CYP4F2 V433M polymorphism on acenocoumarol therapy.
Perez-Andreu V.; Roldan V.; Anton A.I.; Garcia-Barbera N.; Corral J.; Vicente V.; Gonzalez-Conejero R.;
Blood 113:4977-4979(2009)
Cited for: INVOLVEMENT IN CMRES; CHARACTERIZATION OF VARIANT MET-433; CYP4F2 is a vitamin K1 oxidase: An explanation for altered warfarin dose in carriers of the V433M variant.
McDonald M.G.; Rieder M.J.; Nakano M.; Hsia C.K.; Rettie A.E.;
Mol. Pharmacol. 75:1337-1346(2009)
Cited for: FUNCTION; SUBCELLULAR LOCATION; INVOLVEMENT IN CMRES; CHARACTERIZATION OF VARIANT MET-433; CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population.
Borgiani P.; Ciccacci C.; Forte V.; Sirianni E.; Novelli L.; Bramanti P.; Novelli G.;
Pharmacogenomics 10:261-266(2009)
Cited for: INVOLVEMENT IN CMRES; CHARACTERIZATION OF VARIANT MET-433; Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements.
Ross K.A.; Bigham A.W.; Edwards M.; Gozdzik A.; Suarez-Kurtz G.; Parra E.J.;
J. Hum. Genet. 55:582-589(2010)
Cited for: INVOLVEMENT IN CMRES; CHARACTERIZATION OF VARIANT MET-433; Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement: systematic review and meta-analysis.
Danese E.; Montagnana M.; Johnson J.A.; Rettie A.E.; Zambon C.F.; Lubitz S.A.; Suarez-Kurtz G.; Cavallari L.H.; Zhao L.; Huang M.; Nakamura Y.; Mushiroda T.; Kringen M.K.; Borgiani P.; Ciccacci C.; Au N.T.; Langaee T.; Siguret V.; Loriot M.A.; Sagreiya H.; Altman R.B.; Shahin M.H.; Scott S.A.; Khalifa S.I.; Chowbay B.; Suriapranata I.M.; Teichert M.; Stricker B.H.; Taljaard M.; Botton M.R.; Zhang J.E.; Pirmohamed M.; Zhang X.; Carlquist J.F.; Horne B.D.; Lee M.T.; Pengo V.; Guidi G.C.; Minuz P.; Fava C.;
Clin. Pharmacol. Ther. 92:746-756(2012)
Cited for: INVOLVEMENT IN CMRES; CHARACTERIZATION OF VARIANT MET-433;