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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P10632: Variant p.Lys399Arg

Cytochrome P450 2C8
Gene: CYP2C8
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Variant information Variant position: help 399 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Lysine (K) to Arginine (R) at position 399 (K399R, p.Lys399Arg). 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 Similar physico-chemical property. Both residues are large size and basic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 2 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: help 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: help In allele CYP2C8*3; reduces enzymatic activity with paclitaxel as substrate; decreases intrinsic clearance of paclitaxel; reduces enzymatic activity with amodiaquine as substrate. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 399 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 490 The length of the canonical sequence.
Location on the sequence: help YLIPKGTTIMALLTSVLHDD K EFPNPNIFDPGHFLDKNGNF 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: 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 – 490 Cytochrome P450 2C8
Turn 398 – 400



Literature citations
Complete sequencing and characterization of 21,243 full-length human cDNAs.
Ota T.; Suzuki Y.; Nishikawa T.; Otsuki T.; Sugiyama T.; Irie R.; Wakamatsu A.; Hayashi K.; Sato H.; Nagai K.; Kimura K.; Makita H.; Sekine M.; Obayashi M.; Nishi T.; Shibahara T.; Tanaka T.; Ishii S.; Yamamoto J.; Saito K.; Kawai Y.; Isono Y.; Nakamura Y.; Nagahari K.; Murakami K.; Yasuda T.; Iwayanagi T.; Wagatsuma M.; Shiratori A.; Sudo H.; Hosoiri T.; Kaku Y.; Kodaira H.; Kondo H.; Sugawara M.; Takahashi M.; Kanda K.; Yokoi T.; Furuya T.; Kikkawa E.; Omura Y.; Abe K.; Kamihara K.; Katsuta N.; Sato K.; Tanikawa M.; Yamazaki M.; Ninomiya K.; Ishibashi T.; Yamashita H.; Murakawa K.; Fujimori K.; Tanai H.; Kimata M.; Watanabe M.; Hiraoka S.; Chiba Y.; Ishida S.; Ono Y.; Takiguchi S.; Watanabe S.; Yosida M.; Hotuta T.; Kusano J.; Kanehori K.; Takahashi-Fujii A.; Hara H.; Tanase T.-O.; Nomura Y.; Togiya S.; Komai F.; Hara R.; Takeuchi K.; Arita M.; Imose N.; Musashino K.; Yuuki H.; Oshima A.; Sasaki N.; Aotsuka S.; Yoshikawa Y.; Matsunawa H.; Ichihara T.; Shiohata N.; Sano S.; Moriya S.; Momiyama H.; Satoh N.; Takami S.; Terashima Y.; Suzuki O.; Nakagawa S.; Senoh A.; Mizoguchi H.; Goto Y.; Shimizu F.; Wakebe H.; Hishigaki H.; Watanabe T.; Sugiyama A.; Takemoto M.; Kawakami B.; Yamazaki M.; Watanabe K.; Kumagai A.; Itakura S.; Fukuzumi Y.; Fujimori Y.; Komiyama M.; Tashiro H.; Tanigami A.; Fujiwara T.; Ono T.; Yamada K.; Fujii Y.; Ozaki K.; Hirao M.; Ohmori Y.; Kawabata A.; Hikiji T.; Kobatake N.; Inagaki H.; Ikema Y.; Okamoto S.; Okitani R.; Kawakami T.; Noguchi S.; Itoh T.; Shigeta K.; Senba T.; Matsumura K.; Nakajima Y.; Mizuno T.; Morinaga M.; Sasaki M.; Togashi T.; Oyama M.; Hata H.; Watanabe M.; Komatsu T.; Mizushima-Sugano J.; Satoh T.; Shirai Y.; Takahashi Y.; Nakagawa K.; Okumura K.; Nagase T.; Nomura N.; Kikuchi H.; Masuho Y.; Yamashita R.; Nakai K.; Yada T.; Nakamura Y.; Ohara O.; Isogai T.; Sugano S.;
Nat. Genet. 36:40-45(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2); VARIANTS LYS-139 AND ARG-399; Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS LYS-139; VAL-244; MET-264; PHE-269 AND ARG-399; Sequence of a human liver cytochrome P-450 cDNA clone.
Kolyada A.Y.;
Nucleic Acids Res. 18:5550-5550(1990)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 281-490 (ISOFORM 1); VARIANT ARG-399; Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid.
Dai D.; Zeldin D.C.; Blaisdell J.A.; Chanas B.; Coulter S.J.; Ghanayem B.I.; Goldstein J.A.;
Pharmacogenetics 11:597-607(2001)
Cited for: VARIANTS LYS-139; 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;
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.