PMID: 19949922

Cascorbi I, Haenisch S
Pharmacogenetics of ATP-binding cassette transporters and clinical implications.
Methods Mol Biol. 2010;596:95-121., [PubMed]
Sentences
No. Mutations Sentence Comment
52 ABCC1 p.Ala893Ser
X
ABCC1 p.Ala893Ser 19949922:52:894
status: NEW
view ABCC1 p.Ala893Ser details
ABCB1 p.Asn183Ser
X
ABCB1 p.Asn183Ser 19949922:52:669
status: NEW
view ABCB1 p.Asn183Ser details
ABCB1 p.Asn183Ser
X
ABCB1 p.Asn183Ser 19949922:52:670
status: NEW
view ABCB1 p.Asn183Ser details
ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 19949922:52:693
status: NEW
view ABCB1 p.Ser400Asn details
ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 19949922:52:694
status: NEW
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ABCB1 p.Asn21Asp
X
ABCB1 p.Asn21Asp 19949922:52:558
status: NEW
view ABCB1 p.Asn21Asp details
ABCB1 p.Asn21Asp
X
ABCB1 p.Asn21Asp 19949922:52:559
status: NEW
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ABCB1 p.Gln1107Pro
X
ABCB1 p.Gln1107Pro 19949922:52:951
status: NEW
view ABCB1 p.Gln1107Pro details
ABCB1 p.Gln1107Pro
X
ABCB1 p.Gln1107Pro 19949922:52:952
status: NEW
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ABCB1 p.Ser1141Thr
X
ABCB1 p.Ser1141Thr 19949922:52:1006
status: NEW
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ABCB1 p.Ser1141Thr
X
ABCB1 p.Ser1141Thr 19949922:52:1007
status: NEW
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ABCB1 p.Arg492Cys
X
ABCB1 p.Arg492Cys 19949922:52:776
status: NEW
view ABCB1 p.Arg492Cys details
ABCB1 p.Arg492Cys
X
ABCB1 p.Arg492Cys 19949922:52:777
status: NEW
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ABCB1 p.Met986Val
X
ABCB1 p.Met986Val 19949922:52:926
status: NEW
view ABCB1 p.Met986Val details
ABCB1 p.Met986Val
X
ABCB1 p.Met986Val 19949922:52:927
status: NEW
view ABCB1 p.Met986Val details
Functional Significance of ABCB1 SNPs Table6.3 Frequency of ABCB1 genetic variants in Caucasians, position on DNA, putative effect, and frequencies (134) Position Amino acid or effect Frequency of the variant allele 5'-Flanking -2903 T>C 0.02a 5'-Flanking -2410 T>C 0.10a 5'-Flanking -2352 G>A 0.28a 5'-Flanking -1910 T>C 0.10a 5'-Flanking -1717 T>C 0.02a 5'-Flanking -1325 A>G 0.02a 5'-Flanking -934 A>G 0.10a 5'-Flanking -692 T>C 0.10a 5'-Flanking -41 A>G 0.09b IVS 1a -145 C>G 0.02b IVS 1b -129 T>C 0.06b IVS 1b 12 T>C 0.06c IVS 2 -1 G>A 0.09d c. 61 A>G N21D 0.11d IVS 5 -35 G>C Intronic 0.006c IVS 5 -25 G>T Intronic 0.16c IVS 6 +139 C>T Intronic 0.37d c. 548 A>G N183S 0.01e c. 1199 G>A S400N 0.05d c. 1236 C>T Synonymous 0.41d IVS 12 +44 C>T Intronic 0.05d c. 1474 C>T R492C 0.01e IVS 17 -76 T>A Intronic 0.46d IVS 17 +137 A>G Intronic 0.006c c. 2650 C>T Synonymous 0.03e c. 2677 G>T/A A893S/T 0.42d /0.02d c. 2956 A>G M986V 0.005b c. 3320 A>C Q1107P 0.002d c. 3396 C>T Synonymous 0.03c c. 3421 T>A S1141T 0.00c c. 3435 C>T Synonymous 0.54d c. 4030 Synonymous 0.005b c. 4036 Synonymous 0.30b References: a [42], b [26], c [25], d [28], e [23] with lower activity or expression in Caucasians. Login to comment
59 ABCC1 p.Ala893Ser
X
ABCC1 p.Ala893Ser 19949922:59:74
status: NEW
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The missense variant 2677G>T/A coding for the three different amino acids A893S/T exhibits altered transport properties in membrane vesicles from Sf9 insect cells, overexpressing human ABCB1. Login to comment
62 ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 19949922:62:87
status: NEW
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A further rare missense SNP 1199 G>T (frequency 0.05 in Caucasians, (28)) leading to a Ser400Asn amino acid replacement is associated with lower activity and accordingly higher sensitivity against anticancer drugs. Login to comment
76 ABCC1 p.Ala893Ser
X
ABCC1 p.Ala893Ser 19949922:76:394
status: NEW
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ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 19949922:76:278
status: NEW
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ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 19949922:76:279
status: NEW
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ABCB1 p.Gly191Arg
X
ABCB1 p.Gly191Arg 19949922:76:227
status: NEW
view ABCB1 p.Gly191Arg details
ABCB1 p.Gly191Arg
X
ABCB1 p.Gly191Arg 19949922:76:228
status: NEW
view ABCB1 p.Gly191Arg details
Table6.4 Functional significance of ABCB1 genetic variants and relevance for clinical outcome Position Amino acid exchange Effect of variant 5'-Flanking -2410 T>C Decreased mRNAa 5'-Flanking -692 T>C Decreased mRNAa c. 571 G>A G191R Reduced chemotherapy resistanceb c. 1199 G>A S400N Elevated activityc c. 1236 C>T Synonymous Increased imatinib disposition and therapy responsed c. 2677 G>T/A A893S/T In vitro increased vmax ,q no effect on vincristine,e increased imatinib response in CMLd c. 3435 C>T Synonymous Decreased mRNA and protein expression,f, g decreased invitro transport,h no effect on expression and bioavailability of talinolol,i no effect on invitro transport,j, k decreased digoxin bioavailability,l increased etoposid disposition,m no effect on AML or ALL outcome,k better prognosis of multiple myeloma,n better chemotherapy response in breast cancer,o no effect in colon cancerp References: a [42], b [69], c [38], d [53], e [51], f [23], g [64], h [31], i [39], j [135], k [65-67], l [40, 41], m [52], n [68], o [74], p [70, 71], q [36] As mentioned earlier, the first systematic study on ABCB1 genetic variability and its association to expression and bioavailability was the first one, showing an association of 3435C>T with digoxin plasma levels. Login to comment
118 ABCB1 p.Gly191Arg
X
ABCB1 p.Gly191Arg 19949922:118:119
status: NEW
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In a recent study, a novel ABCB1 571G>A missense variant detected in 6.4% of leukemia patients was reported, causing a Gly191Arg amino acid change (69). Login to comment
134 ABCC1 p.Cys43Ser
X
ABCC1 p.Cys43Ser 19949922:134:113
status: NEW
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ABCC1 p.Arg723Gln
X
ABCC1 p.Arg723Gln 19949922:134:151
status: NEW
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ABCC1 p.Thr73Ile
X
ABCC1 p.Thr73Ile 19949922:134:119
status: NEW
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ABCC1 p.Cys1047Ser
X
ABCC1 p.Cys1047Ser 19949922:134:165
status: NEW
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ABCC1 p.Arg633Gln
X
ABCC1 p.Arg633Gln 19949922:134:144
status: NEW
view ABCC1 p.Arg633Gln details
ABCC1 p.Arg230Gln
X
ABCC1 p.Arg230Gln 19949922:134:137
status: NEW
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ABCC1 p.Ala989Thr
X
ABCC1 p.Ala989Thr 19949922:134:158
status: NEW
view ABCC1 p.Ala989Thr details
ABCC1 p.Ser92Phe
X
ABCC1 p.Ser92Phe 19949922:134:125
status: NEW
view ABCC1 p.Ser92Phe details
A thorough investigation on the functional significance of ten nonsynonymous SNPs, leading to amino acid changes C43S, T73I, S92F, T117; R230Q, R633Q, R723Q, A989T, C1047S. Login to comment
135 ABCC1 p.Arg1058Gln
X
ABCC1 p.Arg1058Gln 19949922:135:0
status: NEW
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ABCC1 p.Ser1512Leu
X
ABCC1 p.Ser1512Leu 19949922:135:12
status: NEW
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R1058Q, and S1512L was performed by Létourneau et al. Login to comment
139 ABCC1 p.Ala989Thr
X
ABCC1 p.Ala989Thr 19949922:139:30
status: NEW
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Lowest capacity was found for A989T, caused by a 2965G>A variant. Login to comment
146 ABCC1 p.Gly671Val
X
ABCC1 p.Gly671Val 19949922:146:119
status: NEW
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In a study on genetic determinants of anthracycline-induced cardiomyopathy in non-Hodgkin lymphoma patients, the ABCC1 Gly671Val variant as well as a haplotype of ABCC2 turned out to be significant risk factors. Login to comment
155 ABCC1 p.Cys43Ser
X
ABCC1 p.Cys43Ser 19949922:155:273
status: NEW
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ABCC1 p.Arg723Gln
X
ABCC1 p.Arg723Gln 19949922:155:751
status: NEW
view ABCC1 p.Arg723Gln details
ABCC1 p.Thr73Ile
X
ABCC1 p.Thr73Ile 19949922:155:305
status: NEW
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ABCC1 p.Arg1058Gln
X
ABCC1 p.Arg1058Gln 19949922:155:860
status: NEW
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ABCC1 p.Gly671Val
X
ABCC1 p.Gly671Val 19949922:155:690
status: NEW
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ABCC1 p.Arg433Ser
X
ABCC1 p.Arg433Ser 19949922:155:538
status: NEW
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ABCC1 p.Cys1047Ser
X
ABCC1 p.Cys1047Ser 19949922:155:832
status: NEW
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ABCC1 p.Arg633Gln
X
ABCC1 p.Arg633Gln 19949922:155:653
status: NEW
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ABCC1 p.Val353Met
X
ABCC1 p.Val353Met 19949922:155:500
status: NEW
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ABCC1 p.Ala989Thr
X
ABCC1 p.Ala989Thr 19949922:155:791
status: NEW
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ABCC1 p.Ser1512Leu
X
ABCC1 p.Ser1512Leu 19949922:155:914
status: NEW
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ABCC1 p.Ser92Phe
X
ABCC1 p.Ser92Phe 19949922:155:332
status: NEW
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ABCC1 p.Arg230Asn
X
ABCC1 p.Arg230Asn 19949922:155:404
status: NEW
view ABCC1 p.Arg230Asn details
ABCC2 (Multidrug Resistance-Associated Protein 2) Table 6.5 Frequency of ABCC1 genetic variants in different populations, position on DNA, putative effect, and frequencies (according to (33, 77-80, 136)) Position Amino acid or effect Orientals Caucasians Function c.128G>C C43S 0.01 - Elevateda c. 218C>T T73I 0.00-0.04 - c. 257C>T S92F 0.00 0.00 Decreaseda c. 350C>T T117M - 0.02 (Decreased)a c. 689G>A R230N 0.00 0.00 (Decreased)a c. 816G>A Synonymous - 0.04 c. 825T>C Synonymous - 0.30 c. 1057G>A V353M 0.00 0.005 Elevateda c. 1299G>T R433S - 0.01 Elevated vmax of doxorubicin, decreased transport of LTC4 a,b c. 1684T>C Synonymous - 0.80 c. 1898G>A R633Q - 0.01 (Decreased)a c. 2012G>T G671V - 0.03 Doxorubicine-induced cardiomyopathyc c. 2168G>A R723Q 0.01-0.07 - Decreaseda c. 2965G>A A989T 0.00 0.005 (Decreased)a c. 3140G>C C1047S 0.00 0.00 c. 3173G>A R1058Q 0.01 - c. 4002G>A Synonymous - 0.28 c. 4535C>T S1512L - 0.03 Decreaseda References: a [81], b [77], c [84] an inducible expression of ABCC2, which contributes also to the phenomenon of drug resistance. Login to comment
190 ABCC2 p.Arg768Trp
X
ABCC2 p.Arg768Trp 19949922:190:200
status: NEW
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ABCC2 p.Val417Ile
X
ABCC2 p.Val417Ile 19949922:190:120
status: NEW
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ABCC2 p.Cys1515Tyr
X
ABCC2 p.Cys1515Tyr 19949922:190:691
status: NEW
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ABCC2 p.Ser789Phe
X
ABCC2 p.Ser789Phe 19949922:190:230
status: NEW
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ABCC2 p.Val1188Glu
X
ABCC2 p.Val1188Glu 19949922:190:484
status: NEW
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ABCC2 p.Ala1450Thr
X
ABCC2 p.Ala1450Thr 19949922:190:631
status: NEW
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ABCC2 p.Arg1174His
X
ABCC2 p.Arg1174His 19949922:190:420
status: NEW
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ABCC2 p.Asn1244Lys
X
ABCC2 p.Asn1244Lys 19949922:190:516
status: NEW
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ABCC2 p.Thr486Ile
X
ABCC2 p.Thr486Ile 19949922:190:169
status: NEW
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ABCC2 p.Gln1019His
X
ABCC2 p.Gln1019His 19949922:190:366
status: NEW
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ABCC2 p.Ser1367Cys
X
ABCC2 p.Ser1367Cys 19949922:190:577
status: NEW
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ABCC2 p.Asp883Asn
X
ABCC2 p.Asp883Asn 19949922:190:260
status: NEW
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ABCC2 p.Lys961Arg
X
ABCC2 p.Lys961Arg 19949922:190:284
status: NEW
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ABCC2 p.Arg100Gln
X
ABCC2 p.Arg100Gln 19949922:190:73
status: NEW
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ABCC2 p.Pro19Leu
X
ABCC2 p.Pro19Leu 19949922:190:23
status: NEW
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ABCC2 p.Ser281Asn
X
ABCC2 p.Ser281Asn 19949922:190:96
status: NEW
view ABCC2 p.Ser281Asn details
0.01* (0.00) c. 56 C>T P19L 0.01* c. 234 A>G Synonymous 0.01* c. 299 G>A R100Q 0.01* c. 842 G>A S281N 0.01* c. 1249 G>A V417I 0.13 (0.21) c. 1446 C>G (0.01) c. 1457 C>T T486I 0.03* (0.00) c. 2302 C>T R768W 0.01 (0.00) c. 2366 C>T S789F 0.01 (0.00) c. 2647 G>A D883N 0.01* c. 2882 A>G K961R 0.01* c. 2934 G>A Synonymous 0.05* c. 3039 C>T Synonymous 0.01* c. 3057 G>T Q1019H 0.01* c. 3321 G>T Synonymous 0.01* c. 3521 G>A R1174H 0.01* c. 3542 G>T (0.001) c. 3561 G>A (0.00) c. 3563 T>A V1188E 0.01* (0.05) c. 3732 C>T N1244K 0.01* c. 3972 C>T Synonymous 0.22* (0.34) c. 4100 C>G S1367C 0.01* c. 4290 G>T Synonymous 0.01* c. 4348 G>A A1450T 0.01 (0.00) c. 4488 C>T Synonymous 0.01* c. 4544 G>A C1515Y 0.01* (0.04) association to cholestatic or mixed type hepatitis whereas -24T carriers exhibited more often hepatocellular-type hepatitis after intake of drugs or herbal remedies (96). Login to comment
192 ABCC2 p.Val417Ile
X
ABCC2 p.Val417Ile 19949922:192:24
status: NEW
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A missense SNP 1249G>A (Val417Ile) is located in substrate-binding region of the first transmembrane domain and is associated with lower oral bioavailability and increased residual clearance after intravenous administration of the beta-blocker talinolol, indicating a higher activity of the intestinal transporter (92). Login to comment
210 ABCC2 p.Val417Ile
X
ABCC2 p.Val417Ile 19949922:210:618
status: NEW
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Function and Substrate Specificity Table 6.7 ABCC2 polymorphisms currently described to exhibit a clinical influence ABCC2 polymorphism Effect Clinical impact on Function Reference -1774 G /del 5'-flanking Hepatotoxicity of herbal and conventional drugs Decreased [96] -24C>T 5'-UTR Hepatotoxicity of drugs e.g. diclofenac and herbal remedies Decreased [96, 97] Oral clearance of Mycophenolic acid Decreased [93, 94] Risk of renal failure, renal expression Decreased [90, 95] Bioavailability and side effects of methotrexate Decreased [104] Tumor response and side effects of irinotecan Decreased [105, 106] c.1249G>A V417I Intestinal activity, bioavailability of talinolol Increased [92] Gastrointestinal toxicity of methotrexate Increased? Login to comment
212 ABCC2 p.Cys1515Tyr
X
ABCC2 p.Cys1515Tyr 19949922:212:217
status: NEW
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ABCC2 p.Val1188Glu
X
ABCC2 p.Val1188Glu 19949922:212:78
status: NEW
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[98] c.1446C>G T482T Bioavailability of pravastatin Increased [101] c.3563T>A V1188E Higher protein expression in liver Increased [102] c.3972C>T I1324I Intrahepatic cholestasis in pregnancy Decreased [103] c.4544G>A C1515Y Higher protein expression in liver Increased [102] composed of 655 amino acids (109). Login to comment
224 ABCG2 p.Gln141Lys
X
ABCG2 p.Gln141Lys 19949922:224:41
status: NEW
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ABCG2 p.Val12Met
X
ABCG2 p.Val12Met 19949922:224:23
status: NEW
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Both identified 34G>A (V12M) and 421C>A (Q141K). Login to comment
231 ABCG2 p.Gln141Lys
X
ABCG2 p.Gln141Lys 19949922:231:147
status: NEW
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ABCG2 p.Val12Asn
X
ABCG2 p.Val12Asn 19949922:231:45
status: NEW
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HEK-293 cells, transfected with wild-type or V12N, ABCG2 showed apical staining with an ABCG2 antibody, but high intracellular staining in case of Q141K, suggesting impaired membrane trafficking or incorrect membrane insertion. Login to comment
232 ABCG2 p.Val12Met
X
ABCG2 p.Val12Met 19949922:232:89
status: NEW
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Moreover, decreased transport rates were found in Sf9 insect cells, transfected with the V12M variant (119). Login to comment
239 ABCG2 p.Val12Met
X
ABCG2 p.Val12Met 19949922:239:16
status: NEW
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0.235 c. 34 G>A V12M 0.17 0.04a 0.06b IVS 2 +16 A>G ? Login to comment
242 ABCG2 p.Gln141Lys
X
ABCG2 p.Gln141Lys 19949922:242:71
status: NEW
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ABCG2 p.Gln126*
X
ABCG2 p.Gln126* 19949922:242:17
status: NEW
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ABCG2 p.Gln126*
X
ABCG2 p.Gln126* 19949922:242:17
status: NEW
view ABCG2 p.Gln126* details
0.005 c. 376 C>T Q126stop 0.01 0.00a 0.00b Lack of function c. 421 C>A Q141K 0.35 0.11a 0.02b Reduced activity [120, 124, 137] IVS 5 -16 A>G ? Login to comment
244 ABCG2 p.Ser441Asn
X
ABCG2 p.Ser441Asn 19949922:244:18
status: NEW
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0.015 c. 1322 G>A S441N 0.005 c. 1367 A>G ? Login to comment
245 ABCG2 p.Phe489Leu
X
ABCG2 p.Phe489Leu 19949922:245:18
status: NEW
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0.165 c. 1465 A>G F489L 0.005 c.1492 G>C ? Login to comment
253 ABCG2 p.Val12Asn
X
ABCG2 p.Val12Asn 19949922:253:6
status: NEW
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ABCG2 V12N protein was found to be accumulated intracellulary (120) and always apical expression was observed by Kondo et al. Login to comment
258 ABCG2 p.Val12Met
X
ABCG2 p.Val12Met 19949922:258:15
status: NEW
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Interestingly, V12M was associated with elevated activity compared to the wild-type, whereas ABCG2 with premature stop-codon lacked any activity as expected (37). Login to comment