Table 1.

Characteristics, locations, and effect on DPYD enzyme activity of the different SNPs previously described in the literature

Name (ref.)ExonNucleotideAmino acidFrequency (%)Consequence
SNPs systematically searched for
    DPYD (21) promoter−1590T>C0.5IFNγ-binding site altered, lowered expression
    DPYD 9A (2224)285T>CC29R29Consequence unclear
    DPYD 7 (25)4295-298 del TCATFrameshiftUNonsense, truncated protein, 0 activity
    DPYD 7 (26)111156G>TE386TerUNonsense, truncated protein, 0 activity
    DPYD 7 (24, 27, 28)131679T>GI560SUMissense, FAD site, interference with cofactor binding, no activity
    DPYD 2A, G1A (11)14IVS14 + 1G>AExon 14 skipping,1.5Splice site mutation, uracil-binding site deleted
    DPYD 9B (22)212657G>AR886HUMissense, conformational site modified
    DPYD 9B (10, 27, 29)222846A>TD949VUMissense, direct interference with cofactor binding or electron transport, [4Fe-4S] function altered
    DPYD 10 (10)232983G>TV995FUMissense
SNPs searched for in case of grade 3 to 4 toxicity and upper SNPs negative
    DPYD 10 (28)261C>TR21XUNonsense, truncated protein, no activity
    DPYD 10 (28)262G>AR21QUMissense, no consequence?
    DPYD 10 (30)4257C>TP86LUMissense mutation, direct interference with electron transport, [4Fe-4S] nonfunctional
    DPYD 10 (30)6601A>CS201RUMissense, direct interference with electron transport
    DPYD 10 (30)6632A>GY211CUEnzyme structure altered, enzyme destabilization
    DPYD8 (27)7703C>TR235WUMissense, FAD site affected
    DPYD8 (31)8812 del TFrameshiftTruncated protein, no activity
    DPYD8 (10)101039-1042 del TGFrameshiftUNonsense, NADPH site affected, no activity
    DPYD8 (27)101003G>TV 335LUMissense, NADP site affected
    DPYD8 (30)121475C>TS492LUMissense, FAD site, interference with cofactor-binding, no activity
    DPYD 4 (24)131601G>AS534N0.8Missense, between FAD and uracil-binding site, reduced activity
    DPYD 3 (30)141897delCFrameshiftUStopping codon before uracil-binding site
    DPYD 3 (10)232933A>GH978RUMissense, direct interference with cofactor- binding or electron transport, [4Fe-4S]
  • Abbreviation: U, unreported in the literature.