UniProtKB/Swiss-Prot P10632: Variant p.Ile264Met

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 264 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 Isoleucine (I) to Methionine (M) at position 264 (I264M, p.Ile264Met). 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: Several alleles are found in the human population, contributing to interindividual variations in the therapeutic efficacy and toxicity of a myriad of drugs such as paclitaxel or amodiaquine. The allele shown here is CYP2C8*1 (PubMed:26427316). CYP2C8 genetic variations are associated with altered drug metabolism and adverse drug effects including acute rhabdomyolysis after cerivastatin use [MIM:618018]. Additional information on the polymorphism described.
Variant description: In allele CYP2C8*4; reduces enzymatic activity with paclitaxel as substrate; decreases affinity for amodiaquine. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs1058930 [ dbSNP | Ensembl ]

Sequence information

Variant position: 264 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: IREKVKEHQASLDVNNPRDF I DCFLIKMEQEKDNQKSEFNI 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	1 – 490	Cytochrome P450 2C8
Helix	263 – 273

Literature citations

Characterization of multiple human cytochrome P-450 1 cDNAs. The chromosomal localization of the gene and evidence for alternate RNA splicing.
Okino S.T.; Quattrochi L.C.; Pendurthi U.R.; McBride O.W.; Tukey R.H.;
J. Biol. Chem. 262:16072-16079(1987)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT MET-264; Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily.
Romkes M.; Faletto M.B.; Blaisdell J.A.; Raucy J.L.; Goldstein J.A.;
Biochemistry 30:3247-3255(1991)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT MET-264; Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS LYS-139; VAL-244; MET-264; PHE-269 AND ARG-399; CYP2C8 polymorphisms in Caucasians and their relationship with paclitaxel 6alpha-hydroxylase activity in human liver microsomes.
Bahadur N.; Leathart J.B.; Mutch E.; Steimel-Crespi D.; Dunn S.A.; Gilissen R.; Houdt J.V.; Hendrickx J.; Mannens G.; Bohets H.; Williams F.M.; Armstrong M.; Crespi C.L.; Daly A.K.;
Biochem. Pharmacol. 64:1579-1589(2002)
Cited for: VARIANTS LYS-139; MET-264; PHE-269; SER-390 AND ARG-399; Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population.
Solus J.F.; Arietta B.J.; Harris J.R.; Sexton D.P.; Steward J.Q.; McMunn C.; Ihrie P.; Mehall J.M.; Edwards T.L.; Dawson E.P.;
Pharmacogenomics 5:895-931(2004)
Cited for: VARIANTS LYS-139; MET-264; PHE-269 AND ARG-399; Functional characterization of 12 allelic variants of CYP2C8 by assessment of paclitaxel 6alpha-hydroxylation and amodiaquine N-deethylation.
Tsukada C.; Saito T.; Maekawa M.; Mano N.; Oda A.; Hirasawa N.; Hiratsuka M.;
Drug Metab. Pharmacokinet. 30:366-373(2015)
Cited for: CHARACTERIZATION OF VARIANTS LYS-139; SER-171; GLY-186; MET-223; PRO-238; ARG-247; MET-264; PHE-269; ASN-383; ARG-399 AND VAL-461 DEL; FUNCTION; BIOPHYSICOCHEMICAL PROPERTIES; POLYMORPHISM;