TABLE 3

Summary of the effects of less-well studied ABCG2 SNPs on expression and function

Base ChangeAmino Acid ChangeLocationTest Systems (Cell Lines)Effects on ABCG2Effects on Drug TransportReference
458 C>TT153MNBDCancer cell lines HCT116; blood cells from patients; murine fibroblast PA317 cellsDecreased expression; impaired efflux activity; possible disruption to ATP bindingLower SN-38 resistance; defective urate transportMizuarai et al. (2004); Yoshioka et al. (2007); Stiburkova et al. (2017)
616 A>CI206LNBDHEK293 cells; murine fibroblast PA317 cellsDecreased expression; no effect on effluxNo effects shownVethanayagam et al. (2005); Yoshioka et al. (2007)
623 T>CF208SNBDBlood leukocytes; chronic myeloid leukemia K562 cellsDecreased expression; impaired efflux activity; possible disruption to ATP bindingSensitivity to SN-38 and mitoxantrone; defective porphyrin and TKI transportItoda et al. (2003); Skoglund et al. (2014)
742 T>CS248PLinkerHEK293-Tet-On-cells; Flp-In293 cells; Sf9 cellsSimilar expression; impaired efflux activityLower SN-38 and mitoxantrone resistance; defective porphyrin transportTamura et al. (2006), (2007b); Deppe et al. (2014)
805 C>TP269SLinkerHEK cells; cellular localization monitored in LLC-PK1 cells; Sf9 cellsSimilar expression; impaired efflux activityNo effect on urate transportKondo et al. (2004), Lee et al. (2007), Higashino et al. (2017)
886 G>CD296HLinkerChronic myeloid leukemia K562 cellsDecreased expressionIncreased sensitivity to TKIsSkoglund et al. (2014)
1291 T>CF431LTMH2HEK293-Tet-On-cells; chronic myeloid leukemia K562 cells; Flp-In293 cells; Sf9 cells; murine fibroblast PA317 cellsSimilar expression; impaired efflux activity or drug substrate bindingIncrease sensitivity to SN-38, mitoxantrone, and methotrexate; defective porphyrin transportTamura et al. (2006), (2007b); Yoshioka et al. (2007); Kawahara et al. (2010); Deppe et al. (2014)
1322 G>AS441NTMH2Cellular localization monitored in LLC-PK1 cells; Flp-In293 cells; Sf9 cells; HEK283 cellsDecreased expression; impaired or abrogated efflux activity; change in substrate specificitySensitivity to SN-38 and mitoxantrone; defective porphyrin transport; defective urate transportKondo et al. (2004); Tamura et al. (2006), (2007b); Nakagawa et al. (2008); Sjöstedt et al. (2017)
1465 T>CF489LTMH3HEK293 Tet-On-cells; HEK293 cells; Sf9 cells; Flp-In293 cellsSimilar or reduced expression level; impaired effluxSensitivity to SN-38, mitoxantrone, and methotrexateTamura et al. (2006), (2007b); Deppe et al. (2014); Sjöstedt et al. (2017)
1574 T>GL525RTMH4Sf9 cells; HEK283 cells; chronic myeloid leukemia K562 cellsDecreased expression level;Sensitivity to TKIs; proximal residue M523 is involved in drug recognitionSkoglund et al. (2014); Sjöstedt et al. (2017)
1582 G>AA528TTMH4Chronic myeloid leukemia K562 cellsSimilar expression level to WT; increased efflux activityNo effects to dateSkoglund et al. (2014)
1768 A>TN590YTMH5-6 loopHEK293 cells; murine fibroblast PA317 cells; DNA isolation from liver and intestinal donorsSimilar or increased expressionIncreased sensitivity to mitoxantrone and topotecan; no change in SN-38 pharmacokineticsZamber et al. (2003); Vethanayagam et al. (2005); Yoshioka et al. (2007)
1858 G>AD620NTMH5-6 loopHEK293 cells; chronic myeloid leukemia K562 cells; blood cells; Sf9 cellsAmbiguous; documented increases and decreases in both expression and activityAmbiguous; documented increased sensitivity or no change in sensitivity; defective urate transport?Morisaki et al. (2005); Vethanayagam et al. (2005); Tamura et al. (2006); Skoglund et al. (2014); Stiburkova et al. (2017)

  • HEK293, human embryonic kidney 293.