PMID: 19285158

Fung KL, Gottesman MM
A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function.
Biochim Biophys Acta. 2009 May;1794(5):860-71. Epub 2009 Mar 11., [PubMed]
Sentences
No. Mutations Sentence Comment
145 ABCB1 p.Gly185Val
X
ABCB1 p.Gly185Val 19285158:145:86
status: NEW
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A missense mutation found at position 183 is very close to two amino acids before the G185V mutation site. Login to comment
146 ABCB1 p.Gly185Val
X
ABCB1 p.Gly185Val 19285158:146:5
status: NEW
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ABCB1 p.Gly185Val
X
ABCB1 p.Gly185Val 19285158:146:86
status: NEW
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A missense mutation found at position 183 is very close to two amino acids before the G185V mutation site. Login to comment
147 ABCB1 p.Gly185Val
X
ABCB1 p.Gly185Val 19285158:147:5
status: NEW
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This G185V mutation has been identified in drug-resistant cell lines, but not in humans. Login to comment
151 ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 19285158:151:102
status: NEW
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ABCB1 p.Asn21Asp
X
ABCB1 p.Asn21Asp 19285158:151:70
status: NEW
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ABCB1 p.Phe103Leu
X
ABCB1 p.Phe103Leu 19285158:151:85
status: NEW
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ABCB1 p.Ala999Thr
X
ABCB1 p.Ala999Thr 19285158:151:139
status: NEW
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A study in our lab showed that common polymorphisms of MDR1 at 61ANG (N21D), 307TNC (F103L), 1199GNA (S400N), 2677GNT (A893S) and 2995GNA (A999T) do not change the transport of four MDR1 substrates when expressed at high levels in human cells [66]. Login to comment
152 ABCC1 p.Ala893Ser
X
ABCC1 p.Ala893Ser 19285158:152:119
status: NEW
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ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 19285158:152:79
status: NEW
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ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 19285158:152:102
status: NEW
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ABCB1 p.Asn21Asp
X
ABCB1 p.Asn21Asp 19285158:152:70
status: NEW
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ABCB1 p.Asn21Asp
X
ABCB1 p.Asn21Asp 19285158:152:73
status: NEW
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ABCB1 p.Phe103Leu
X
ABCB1 p.Phe103Leu 19285158:152:85
status: NEW
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ABCB1 p.Ala999Thr
X
ABCB1 p.Ala999Thr 19285158:152:139
status: NEW
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ABCB1 p.Ser1141Thr
X
ABCB1 p.Ser1141Thr 19285158:152:107
status: NEW
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ABCB1 p.Arg669Cys
X
ABCB1 p.Arg669Cys 19285158:152:86
status: NEW
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ABCB1 p.Val1251Ile
X
ABCB1 p.Val1251Ile 19285158:152:115
status: NEW
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A study in our lab showed that common polymorphisms of MDR1 at 61ANG (N21D), 307TNC (F103L), 1199GNA (S400N), 2677GNT (A893S) and 2995GNA (A999T) do not change the transport of four MDR1 substrates when expressed at high levels in human cells [66]. Login to comment
153 ABCC1 p.Ala893Ser
X
ABCC1 p.Ala893Ser 19285158:153:93
status: NEW
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ABCC1 p.Ala893Thr
X
ABCC1 p.Ala893Thr 19285158:153:100
status: NEW
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ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 19285158:153:79
status: NEW
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ABCB1 p.Asn21Asp
X
ABCB1 p.Asn21Asp 19285158:153:73
status: NEW
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ABCB1 p.Ser1141Thr
X
ABCB1 p.Ser1141Thr 19285158:153:96
status: NEW
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ABCB1 p.Ser1141Thr
X
ABCB1 p.Ser1141Thr 19285158:153:107
status: NEW
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ABCB1 p.Arg669Cys
X
ABCB1 p.Arg669Cys 19285158:153:74
status: NEW
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ABCB1 p.Arg669Cys
X
ABCB1 p.Arg669Cys 19285158:153:86
status: NEW
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ABCB1 p.Leu662Arg
X
ABCB1 p.Leu662Arg 19285158:153:67
status: NEW
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ABCB1 p.Val1251Ile
X
ABCB1 p.Val1251Ile 19285158:153:115
status: NEW
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ABCB1 p.Met89Thr
X
ABCB1 p.Met89Thr 19285158:153:61
status: NEW
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ABCB1 p.Trp1108Arg
X
ABCB1 p.Trp1108Arg 19285158:153:88
status: NEW
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A recent study by Gow et al. suggested that all of the SNPs they tested (N21D, S400N, R669C, A893S, A893T, S1141T, V1251I) produced small changes which in most cases are not statistically significant [59]. Login to comment
154 ABCC1 p.Ala893Ser
X
ABCC1 p.Ala893Ser 19285158:154:81
status: NEW
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ABCB1 p.Ser1141Thr
X
ABCB1 p.Ser1141Thr 19285158:154:96
status: NEW
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ABCB1 p.Arg669Cys
X
ABCB1 p.Arg669Cys 19285158:154:74
status: NEW
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ABCB1 p.Leu662Arg
X
ABCB1 p.Leu662Arg 19285158:154:67
status: NEW
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ABCB1 p.Met89Thr
X
ABCB1 p.Met89Thr 19285158:154:61
status: NEW
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ABCB1 p.Trp1108Arg
X
ABCB1 p.Trp1108Arg 19285158:154:88
status: NEW
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Another study using a yeast host to express human MDR1 SNPs (M89T, L662R, R669C, A893S, W1108R, S1141T) showed increased resistance to anthracyclines, actinomycin D and valinomycin. Login to comment
185 ABCC1 p.Ala893Ser
X
ABCC1 p.Ala893Ser 19285158:185:27
status: NEW
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ABCC1 p.Ala893Thr
X
ABCC1 p.Ala893Thr 19285158:185:68
status: NEW
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The occurrence of 2677GNT (A893S) is far more frequent than G2677A (A893T). Login to comment
226 ABCB1 p.Asn21Asp
X
ABCB1 p.Asn21Asp 19285158:226:892
status: NEW
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Protein function is different depending on substrate use 1236T-3435T 2677T-3435T 1236T-2677T-3435T 1236T-2677T-3435A Hung CC et al. 2008 [93] Flp-In HEK-293 Stable No difference 1236T-2677A Rhodamine 123 Calcein-AM, phenytoin, cyclosporine A, phenobarbital valproic acid, lamotrigine, carbamazepine, gabapentin, levetiracetam Certain inhibitors against Rhodamine 123 transport are less effective in double haplotype and TTT haplotype 1236T-2677T 1236T-3435T 2677A-3435T 2677T-3435T 1236T-2677A-3435T 1236T-2677T-3435T Salama NN et al. 2006 [91] LLC-PK1 Stable No apparent difference 1236T-2677T Rhodamine 123, vincristine, vinblastine Single or haplotype mutations had significant decrease in MDR1 function 1236T-3435T 2677T-3435T 1236T-2677T-3435T GOW JM et al. 2008 [59] HEK-293T Transient No difference 1236T-2677T-3435T Calcein-AM, cyclosporine A, BODIPY-FL-paclitaxel TTT haplotype with N21D mutation reduces MDR1 function with BODIPY-FL-paclitaxel but not Calcein-AM. Login to comment
227 ABCB1 p.Asn21Asp
X
ABCB1 p.Asn21Asp 19285158:227:891
status: NEW
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Protein function is different depending on substrate use 1236T-3435T 2677T-3435T 1236T-2677T-3435T 1236T-2677T-3435A Hung CC et al. 2008 [93] Flp-In HEK-293 Stable No difference 1236T-2677A Rhodamine 123 Calcein-AM, phenytoin, cyclosporine A, phenobarbital valproic acid, lamotrigine, carbamazepine, gabapentin, levetiracetam Certain inhibitors against Rhodamine 123 transport are less effective in double haplotype and TTT haplotype 1236T-2677T 1236T-3435T 2677A-3435T 2677T-3435T 1236T-2677A-3435T 1236T-2677T-3435T Salama NN et al. 2006 [91] LLC-PK1 Stable No apparent difference 1236T-2677T Rhodamine 123, vincristine, vinblastine Single or haplotype mutations had significant decrease in MDR1 function1236T-3435T 2677T-3435T 1236T-2677T-3435T GOW JM et al. 2008 [59] HEK-293T Transient No difference 1236T-2677T-3435T Calcein-AM, cyclosporine A, BODIPY-FL-paclitaxel TTT haplotype with N21D mutation reduces MDR1 function with BODIPY-FL-paclitaxel but not Calcein-AM. Login to comment
341 ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 19285158:341:57
status: NEW
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Several amino acid residues around this SNP (e.g., Y401, S400N) are essential for ATP-binding and ATP hydrolysis [42,49]. Login to comment
342 ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 19285158:342:57
status: NEW
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Several amino acid residues around this SNP (e.g., Y401, S400N) are essential for ATP-binding and ATP hydrolysis [42,49]. Login to comment
351 ABCB1 p.Gly830Val
X
ABCB1 p.Gly830Val 19285158:351:68
status: NEW
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ABCB1 p.Ile849Met
X
ABCB1 p.Ile849Met 19285158:351:75
status: NEW
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Nevertheless, mutation studies have identified several amino acids (G830V, I849M) that could change the kinetics of drug-induced ATPase activity [42,116]. Login to comment
352 ABCB1 p.Gly830Val
X
ABCB1 p.Gly830Val 19285158:352:68
status: NEW
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ABCB1 p.Ile849Met
X
ABCB1 p.Ile849Met 19285158:352:75
status: NEW
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Nevertheless, mutation studies have identified several amino acids (G830V, I849M) that could change the kinetics of drug-induced ATPase activity [42,116]. Login to comment