ABCMdb

ABCB11 p.Ala865Val

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Publications

PMID: 12717091 [PubMed] Goto K et al: "Bile salt export pump gene mutations in two Japanese patients with progressive familial intrahepatic cholestasis."

No. Sentence Comment

82 Differences between BSEP mRNA sequence of Case 1 and registered sequence, and results of genetic analyses performed on family members Nucleotide number of reference sequence Nucleotide substitutions from reference sequence Type of nucleotide Amino acid substitutions from reference sequence Familial investigation of nucleotide substitutions Frequency of alleles of non-PFIC cases 1015 G → C G Val → Leu 0/10 homo C (V339L) 10/10 1331 T → C T Val → Ala 2/10 hetero C (V444A) 8/10 1723 C → T C Arg → Stop Patient: CT Father: CT 10/10 hetero T (R575X) Mother: CC Brother: CC 0/10 1907 A → G A Glu → Gly Patient: AG Father: AA 110/110 hetero G (E636G) Mother: AG Brother: AA 0/100 2594 C → T C Ala → Val 106/110 hetero T (A865V) 4/110 3084 A → G A (-) 5/10 homo G 5/10 A, adenine; T, thymine; G, guanine; C, cytosine; Val, V, valine; Leu, L, Leucine; Ala, A, alanine; Arg, R, arginine; Glu, E, glutamate; Gly, G, glycine; homo, homozygote; hetero, heterozygote. Login to comment

PMID: 16763017 [PubMed] Lang T et al: "Genetic variability, haplotype structures, and ethnic diversity of hepatic transporters MDR3 (ABCB4) and bile salt export pump (ABCB11)."

No. Sentence Comment

108 Of 19 genetic variants in coding and noncoding exons, 8 TABLE 4 Continued Variant ID 5Ј Sequence Genetic Variation 3Ј Sequence Region Amino Acid Change CA AA JA Total n % n % n % n 48 TTTTGTAGC g.73233AϾG ATGGGCTGT Exon 20 A804A 200 0.0 66 93.9 96 0.0 362 1.1 49 CTACAGATG g.73505CϾT TTCCCAAGT Exon 21 A865V 178 0.0 74 0.0 82 2.4 334 0.6 73 TGGGAGGGG g.73539AϾC AATAGAAGT Intron 21 176 0.6 74 0.0 84 0.0 334 0.3 74 TGGTAAAAG g.81650CϾT GACTGTGTG Intron 21 196 0.0 86 1.2 94 0.0 376 0.3 75 GTCACGAAA g.82653GϾA GAGTTATTT Intron 22 136 0.0 90 0.0 46 2.2 272 0.4 50 GTTATTTCT g.82665GϾA CCCTTGTAT Intron 22 202 0.0 92 6.5 82 0.0 376 1.6 76 AGGAGAGGC g.82759GϾA GTTCATTGA Exon 23 R958Q 202 0.0 92 0.0 94 1.1 388 0.3 77 CAATATTTA g.82829CϾT GGATTCTGC Exon 23 Y981Y 200 0.0 92 1.1 94 0.0 386 0.3 78 GTTTATTGC g.82871GϾA AATTCTGCT Exon 23 A995A 200 0.0 92 1.1 94 0.0 386 0.3 51 ACTGAGTGC g.85620AϾG ACAGCTCTT Exon 24 A1028A 194 54.1 76 26.3 90 47.8 360 47.8 79 CTATGCAGC g.85774CϾA ATAAAAAAG Intron 24 194 0.0 76 0.0 90 1.1 360 0.3 80 GCAAACTAA g.85848CϾG ACAAGAACA Intron 24 194 0.0 76 1.3 90 0.0 360 0.3 52 TAAATTTAC g.87308AϾG TATCCTTCT Exon 25 T1086T 186 0.0 76 7.9 82 0.0 344 1.7 53 CAATCATGC g.94270AϾG TCTTTGCAT Intron 27 172 55.2 64 75.0 94 51.1 330 48.2 81 CCAGAACGC g.94387GϾA GATATCATT Exon 28 A1283A 194 0.0 64 0.0 94 1.1 352 0.3 82 TCCCAGCAG g.94582GϾA AGGGATTGT Exon 28 192 0.0 26 0.0 88 1.1 306 0.3 n, number of alleles analyzed (number of subjects times 2); %, allele frequencies for Caucasians (CA), African Americans (AA), and Japanese (JA). Login to comment
116 Two Caucasian-specific variants in exon 13 (c.1331TϾC; 59.4%) and exon 17 (c.2029AϾG; 4.2%) coded for amino acid substitutions p.V444A and p.M677V; one variant, detected in exon 16 (c.1846CϾG, 2.2%) in the African-American population sample, resulted in protein sequence alteration p.R616G; and the Japanese-specific exon 21 variant c.2594CϾT (2.4%) resulted in amino acid substitution p.A865V (Table 4). Login to comment
166 The most common ABCB11 protein-altering polymorphism was p.V444A, which was frequently observed in all groups [ABCB11 p.M677V was present in both the Caucasian (4.2%,) and the African-American (14%) population sample and p.A865V was only found in Japanese samples]. Login to comment
177 Amino Acid Change Scoring Systems for Nonsynonymous Variants Grantham SIFT PolyPhen Blosum62 EC/EU MDR3 D87E 45 1.00 0.48 2 EC P95S 74 0.48 0.87 -1 EC T175A 58 0.01 0.72 -1 EC I367V 29 0.23 0.96 3 EC E450G 98 0.01 0.13 -2 EC R590Q 43 0.01 2.51 1 EC R652G 125 0.36 1.47 -2 EU E1099G 98 0.04 1.58 -2 EC BSEP I206V 29 1.00 0.23 3 EU V284A 64 0.13 0.43 -2 EC R299K 26 1.00 0.38 2 EU V444A 64 0.63 0.78 -2 EC R616G 125 0.01 3.16 -2 EC T619A 58 0.00 1.78 -1 EC M677V 21 0.29 0.82 1 EU R698H 29 0.30 0.57 0 EC A865V 64 0.02 1.12 0 EC R958Q 43 0.04 0.24 1 EU neutral mutation model (Tajima, 1989). Login to comment

PMID: 17181454 [PubMed] Sakurai A et al: "Prediction of drug-induced intrahepatic cholestasis: in vitro screening and QSAR analysis of drugs inhibiting the human bile salt export pump."

No. Sentence Comment

120 H2N COOH S56L G238V G260D C336S L339V V444A K461E D482G T923P K930X G982R R1090X R1153C Outside Inside R1268Q A1228VE1186K R1128H R1057X R1050C A926P A865V R698H E636G M677V S593R E592Q N591S R575XA570T Q558H I498T R432T R415Q R299K E297G V284A I206V S194P E186G cholestasis Expert Opin. Drug Saf. (2007) 6(1) Table 1. Login to comment
125 [40] - 21 2594 C→T Ala865Val PFIC2? Login to comment

PMID: 18692205 [PubMed] Chen HL et al: "Diagnosis of BSEP/ABCB11 mutations in Asian patients with cholestasis using denaturing high performance liquid chromatography."

No. Sentence Comment

7 Polymorphisms V444A and A865V, with an allele frequencies 75.6% and 0.6%, respectively, were found in our population. Login to comment
75 Analysis of V444A and A865V in Patients with Neonatal Cholestasis and PFIC To investigate whether the 2 nonsynonymous polymorphisms found in our population have functional consequences and affect disease presentation, we analyzed the allele frequencies of polymorphisms in 21 patients with PFIC/BRIC, 23 patients with neonatal cholestasis other than PFIC, and 88 control subjects with chronic nonsymptomatic HBV. Login to comment
76 These samples were tested using DHPLC analysis of exons 13 and 21, followed by direct sequencing to identify the V444A and A865V polymorphisms. Login to comment
92 2720CϾT (p.A865V) were detected in a number of our patients and parents.19 We then analyzed these two polymorphic sites with DHPLC followed by sequencing analysis in 21 patients with PFIC/BRIC, 23 patients with neonatal cholestasis other than PFIC, and 88 control patients. Login to comment
95 Distributions of V444A and A865V polymorphisms, as well as allele frequencies, are shown in Table III. We found that V444A was a more prevalent polymorphism in control patients, and had an allele frequency of 75.6%. Login to comment
97 There was a trend for a higher frequency of A865V in patients with PFIC/BRIC (9.5%) and neonatal cholestasis (8.7%) than in control subjects (1.1%, P ϭ .094 and .108, respectively) but without statistical significance. Login to comment
98 All of the patients with A865V also carried the homozygous V444A polymorphism. Login to comment
99 However, because the number of patients carrying A865V was small, it is not conclusive whether these differences make any clinical significance. Login to comment
100 While analyzing patients for A865V polymorphism, another novel missense mutation c.2479CϾA (p.L827I), located in exon 21, was found in 1 patient with neonatal cholestasis with a favorable outcome. Login to comment
104 Comparing our results with previously reported large scale genetic analysis of ABCB11 variations in healthy Caucasians, African Americans, and Japanese subjects,19 the missense mutations found in our study were not reported in all the 3 populations. In the same study, V444A and A865V were the only nonsynonymous polymorphisms found in Japanese population, which was consistent with our findings. Login to comment
108 The SIFT results indicated that all of the missense mutations (except polymorphisms V444A and A865V) may affect protein function. Login to comment
123 Interestingly, although our patients had mutations distinct from patients in Western countries, there Table III. Distribution of V444A and A865V polymorphisms and allele frequencies in Taiwanese patients and control subjects PFIC/BRIC Neonatal cholestasis (non-PFIC) Control P1 P2 P3 V444A n ϭ 21 n ϭ 23 n ϭ 88 0.798 0.508 0.806 TT 2 (9.5%) 2 (8.7%) 5 (5.7%) TC 8 (38.1%) 11 (47.8%) 33 (37.5%) CC 11 (52.4%) 10 (43.5%) 50 (56.8%) Allele frequency T % 12 (28.6%) 15 (32.6%) 43 (24.4%) 0.693 0.264 0.818 C % 30 (71.4%) 31 (67.4%) 133 (75.6%) A865V n ϭ 21 n ϭ 23 n ϭ 88 0.094 0.108 1.000 CC 19 (90.5%) 21 (91.3%) 87 (98.9%) CT 2 (9.5%) 2 (8.7%) 1 (1.1%) TT 0 (0.0%) 0 (0.0%) 0 (0.0%) Allele frequency C % 40 (95.2%) 44 (95.7%) 175 (99.4%) 0.096 0.110 1.000 T % 2 (4.8%) 2 (4.3%) 1 (0.6%) P1: Comparisons between PFIC/BRIC vs control. Login to comment
128 Prediction of functional consequences of nonsynonymous mutations and polymorphisms in ABCB11 found in Asian patients Amino acid change SIFT PolyPhen (PSIC score) EC/EU M183V 0.02 1.45 EC V284L 0.02 1.87 EC R303K 0.00 0.38 EC V444A 0.76 0.60 EC R487H 0.01 0.65 EC L827I 0.01 1.23 EC A865V 0.10 0.76 EC G1004D 0.00 1.97 EC SIFT, Sorting intolerant from tolerant (SIFT scores Ͻ0.05 indicate evolutionarily conserved amino acids, and mutation of these residues are predicted to be deleterious); PolyPhen, polymorphism phenotyping (a PSIC score Ͻ0.5 denotes benign variants, between 1.5 and 2 is possibly damaging, and Ͼ2 is probably damaging); EC, evolutionarily conserved; EU, evolutionarily unconserved. Login to comment
148 Because the number of patients tested in this study is small, it is not conclusive whether V444A or A865V plays roles in PFIC or neonatal cholestasis. Login to comment
165 V444A and A865V are nonsynonymous polymorphisms found in ABCB11 exons in our population, and their association with pediatric cholestatic diseases is not clear. Login to comment

PMID: 19571440 [PubMed] Kim SR et al: "Genetic variations of the ABC transporter gene ABCB11 encoding the human bile salt export pump (BSEP) in a Japanese population."

No. Sentence Comment

41 The three known nonsynonymous variations, 896GÀA (Arg299Lys), 1331CÀT (Ala444Val), and 2594CÀT (Ala865Val), were detected at 0.004, 0.267, and 0.004 frequencies, respectively, which are similar to the previously reported Japanese data.7) One variation, 1331CÀT (Ala444Val), was found 14 residues upstream of the Walker A motif in the NBF1 domain in the large cytoplasmic loop between TMD6 and TMD7. Login to comment
48 Summary of ABCB11 variations detected in this study SNP ID Reference Location Position Nucleotide change Amino acid change Frequency This Study dbSNP (NCBI) NT_005403.16 From the translational initiation site or from the end of the nearest exonb MPJ6_AB11001 rs4148772 7, 8 Intron 1 20084130 IVS1－50 ACTTTGATTAAAG/AAAGAAAGAAGAG 0.058 MPJ6_AB11002 rs10199694 Intron 3 20082623 IVS3＋83 AAGCAGAGAATAC/TTTTCATGCACAT 0.058 MPJ6_AB11003 rs4148775 8 Intron 3 20080475 IVS3－193 TGAGATTGAGCTA/GTACTGAAATCTC 0.225 MPJ6_AB11004 rs4148776 7, 8 Intron 3 20080300 IVS3－18 GTCTTTAAATCCT/CTATGTTTTTCTC 0.058 MPJ6_AB11005 rs3815675 7, 8 Exon 4 20080273 108 CAGGTTACAAGAT/CGAGAAGAAAGGT Asp36Asp 0.225 MPJ6_AB11006a Intron 4 20079560 IVS4－122 CACTCAATTAAGG/ATGATTCCCATGA 0.029 MPJ6_AB11007 7 Intron 4 20079512 IVS4－74 TGAGAATCTAGTA/TACTAAATTAAGT 0.021 MPJ6_AB11008 rs4148777 7, 8 Exon 5 20079319 270 GACAGATGTTTTT/CATTGACTACGAC Phe90Phe 0.058 MPJ6_AB11009a Exon 5 20079310 279 TTTTATTGACTC/TGACGTTGAGTTA Tyr93Tyr 0.004 MPJ6_AB11010a Exon 5 20079228 361 AGTTCCCTCAACC/AAGAACATGACAA Gln121Lys 0.004 MPJ6_AB11011a Intron 5 20062886 IVS5－236 ATATGCATATTTT/CCTGTGATTGGTA 0.004 MPJ6_AB11012 7 Intron 6 20062500 IVS6＋63 ACTACAATGAGAT/GGCAATGTGTTGC 0.017 MPJ6_AB11013a Intron 7 20059917 IVS7－107 ATCCAAGGGTGAT/CAGGGATAGAGAG 0.004 MPJ6_AB11014a Exon 8 20059755 667 CTTTTCATTCAGC/TGCATGACCTCGA Arg223Cys 0.004 MPJ6_AB11015 rs2287614 8 Intron 8 20056962 IVS8－109 GTTACAGTGAGAA/CTCTAATATTGTA 0.058 MPJ6_AB11016 rs2287615 8 Intron 8 20056940 IVS8－87 GTATTAAACCCAT/AGCCACATGTTAA 0.267 MPJ6_AB11017 rs2287616 7, 8 Exon 9 20056830 807 GTTTACGGACTAT/CGAGCTGAAGGCC Tyr269Tyr 0.267 MPJ6_AB11018 rs2287617 7 Exon 9 20056741 896 GTGGTGAGAAAAG/AAGAGGTTGAAAG Arg299Lys 0.004 MPJ6_AB11019 rs4148780 8 Intron 9 20056621 IVS9＋108 TCTGTGGCCTCCA/GGAGGAAGTACTT 0.058 MPJ6_AB11020 rs2287618 7 Intron 9 20052227 IVS9－15 ATTGACTCAAGCG/ATTTTGTCTTCAC 0.217 MPJ6_AB11021a Intron 11 20045737 IVS11＋57 GGGGGTGGGGCAC/AAGAATGAACTCC 0.004 MPJ6_AB11022a Intron 11 20045731 IVS11＋63 GGGGCACAGAATG/AAACTCCTGAAGA 0.004 MPJ6_AB11023a Intron 11 20042655 IVS11－40 TTGTGCATCTTAG/CTTTGAGTTTACA 0.004 MPJ6_AB11024a Exon 12 20042565 1248 GTTGGATCGAATC/AAAGGGTGAAATT Ile416Ile 0.008 MPJ6_AB11025 rs4148783 8 Intron 12 20042389 IVS12＋116 GTAATAGGGAATG/AGAGGTGTCTTTC 0.250 MPJ6_AB11026a Intron 12 20042383 IVS12＋122 GGGAATGGAGGTG/ATCTTTCTCTGAA 0.062 MPJ6_AB11027 rs55669065 Intron 12 20039861 IVS12－93 CACACAGACACCG/AAGTATCAACACA 0.012 MPJ6_AB11028 rs2287622 7, 8 Exon 13 20039746 1331 ACCTCAACATGGC/TCATTAAACCAGG Ala444Val 0.267 MPJ6_AB11029 rs2287623 7, 8 Intron 13 20039573 IVS13＋70 ATATTGATCAAAT/CAGAAAGGTGTAG 0.237 MPJ6_AB11030 rs2389605 Intron 13 20039469 IVS13＋174 TAACAGTGTTCAA/GTGAATAACCAGT 0.237 MPJ6_AB11031 rs4148786 8 Intron 13 20038064_ 20038065 IVS13－87_－86 CTCTATTTTTTC-/CTGCCCATTGGTC 0.004 MPJ6_AB11032a Exon 14 20037953 1460 GCCATGACATTCG/TCTCTCTTAACAT Arg487Leu 0.004 MPJ6_AB11033a Exon 14 20037907 1506 TGGGATAGTGGAG/ACAAGAGCCAGTT Glu502Glu 0.004 MPJ6_AB11034 7 Exon 14 20037808 1605 TGCCAAGGAGGCC/TAATGCCTACAAC Ala535Ala 0.008 MPJ6_AB11035 rs2241340 7, 8 Intron 14 20037743 IVS14＋32 CCTGGGAGAAACC/TAAGAGGTCATAG 0.237 MPJ6_AB11036 rs2241341 8 Intron 14 20037695 IVS14＋80 TACACATTTCTTT/CTCGTATGATTCC 0.237 MPJ6_AB11037 rs55868238 Intron 14 20037647 IVS14＋128 TGTTTTAGTTTCA/-TGCCTGAAAAAG 0.062 MPJ6_AB11038 rs2193831 8 Intron 14 20036295 IVS14－152 AGACAATAACCCA/GTCTGGGGAAGGG 0.237 MPJ6_AB11039 rs2389612 8 Intron 15 20035603 IVS15－124 AATGTCTGCACAG/ACCTATTTAAGAA 0.237 MPJ6_AB11040 rs4148795 8 Intron 18 20030037 IVS18＋97 TTTTCTAGGTATA/GTATCTAGCAGTG 0.417 MPJ6_AB11041 rs4148796 8 Intron 18 20030036 IVS18＋98 TTTCTAGGTATAT/CATCTAGCAGTGT 0.417 MPJ6_AB11042 rs853772 7, 8 Intron 18 20024073 IVS18－17 TGATTAATATAAA/CCCTCTCTCTGCT 0.412 MPJ6_AB11043 rs853773 8 Intron 19 20023765 IVS19＋127 ATCTCTAAAGAAC/TGAAAAATTTCCT 0.396 MPJ6_AB11044 7 Exon 21 20010549 2594 TTGCTACAGATGC/TTTCCCAAGTTCA Ala865Val 0.004 MPJ6_AB11045a Intron 21 20010502 IVS21＋31 AATAGAAGTATAT/GTAACTGCATTGG 0.004 MPJ6_AB11046 rs11568379 Intron 21 20002386 IVS21－25 TGTGTCTGAGACG/AGGTTGATTGCTT 0.054 MPJ6_AB11047a Intron 22 20002132 IVS22＋26 TCTAATTTTCCCA/GTTCCTCATGGCT 0.004 MPJ6_AB11048a Intron 22 20002091 IVS22＋67 AACTGTTAAAAAC/TGAGTAGTACGAA 0.004 MPJ6_AB11049 rs497692 7, 8 Exon 24 19998434 3084 TGTACTGAGTGCG/AACAGCTCTTGGA Ala1028Ala 0.442 MPJ6_AB11050 7 Intron 24 19998280 IVS24＋25 ATACTATGCAGCC/AATAAAAAAGGAT 0.004 MPJ6_AB11051a Intron 25 19996478 IVS25＋115 CTTGCCTAAGGCA/CCTTACCCCATGC 0.042 MPJ6_AB11052 rs7561903 Intron 26 19992983 IVS26＋101 CTGAAAATCCCAA/CATCCAAAATGTT 0.104 MPJ6_AB11053a Intron 26 19992965 IVS26＋119 AAATGTTCCAAAA/GTTCAAAAATTTT 0.004 MPJ6_AB11054a Intron 27 19989910 IVS27－160 CACTGATGCATTG/ACATTCAGGGAAT 0.004 MPJ6_AB11055 rs579275 7, 8 Intron 27 19989784 IVS27－34 GAGCAATCATGCG/ATCTTTGCATCAA 0.437 MPJ6_AB11056 rs473351 8, 15 3?-UTR 19989314 4202 (*236)c ACTAGGGTCCATG/ATGAGGGAAAACC 0.054 MPJ6_AB11057 rs3732038 3?-UTR 19989269 4247 (*281)c GCCACCACTCAGT/GGCTTCTCTGTGC 0.004 MPJ6_AB11058 rs495714 8 3?-UTR 19989182 4334 (*368)c AACTCCTCAAGGA/GCAGAGAACTGTC 0.437 MPJ6_AB11059 rs496550 8 3?-UTR 19989130 4386 (*420)c AGAGGCGGGTCTG/ATAACAGGCAATC 0.437 a Novel variations detected in this study. 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51 280 Su-Ryang KIM, et al. 281281Genetic Variations of ABCB11 in Japanese quency in Japanese (0.196-0.267) is slightly lower than that in Caucasians (0.405) and African-Americans (0.344) (described as g.44308TÀC [Val444Ala] in a previous paper).7) Two other known variations, 896GÀA (Arg299Lys) and 2594CÀT (Ala865Val), were detected only in the Japanese population at allele frequencies of 0.010 for 896GÀA and 0.024 for 2594CÀT, respectively.7) Both variations are located in the cytoplasmic loops between TMD4 and TMD5 and between TMD8 and TMD9. Login to comment

PMID: 22795478 [PubMed] Kubitz R et al: "The bile salt export pump (BSEP) in health and disease."

No. Sentence Comment

185 PFIC BRIC/NFC ICP Other liver diseases Genetic variants without disease association Missense mutations M1V C336S D549V L1055P E135K E137K T87R V43I S701P G19R W342G G556R C1083Y E137K L198P M123T S56L L712L L50S A382G G562D A1110E E186G E297G S194P Q121K A865D M62K R387H A570T S1114R L198P R415Q L198P R128H A865G C68Y A390P L581F G1116E E297G V444A G260D I206V S874P C107R G410D A588V G1116F G374S D482G E297K V284A I939M I112T L413W S593R G1116R A390P N591S V444A G295C R958Q W114R I420T I627T S1120N R432T T655I T510T G295R F959C Y157C D440E E636G R1128C V444A T655I G295S F959V A167T G455E R698C S1144R I498T D676Y R299K T965S A167V K461E S699P R1153C A570T P710P R303K F971L I182K T463I E709K R1153H T586I L827I L339V F971Y M183T Q466K G758R S1154P G648V G855R H423R L1006F M183V R470Q G766R N1173D T655I E1186K V444A N1009H G188W Y472C Y818F T1210P T923P V444D K1145N M217R V481E R832C N1211D A926P V444G I1183T R223C D482G R832H V1212F R948C A459V S226L R487H T859R R1231Q G1004D I468I G238V R487P A865V R1231W R1050C R487L T242I N490D Q869P L1242I G1116R Q546K A257G I498T G877R D1243G R1128H Q558H V284L G499E S901R R1268Q L1197G E592Q E297G I512T R948C A1283V R1231Q V597M R303G N515T N979D G1292V R616G R303K R517H G982R G1298R T619A Q312H F540L G1004D M677L R313S I541L T1029K M677V G327E I541T G1032R R696Q W330R F548Y A1044P R698H Nonsense mutations (premature stop-codons) S25X Y472X Y772X R1090X E96X W493X Q791X V1147X W330X R520X R928X Q1215X Y354X I528X Y1041X R1235X R415X R575X R1057X E1302X R470X Q702X Q1058X Table 1 (Continued) PFIC BRIC/NFC ICP Other liver diseases Genetic variants without disease association Splice site mutations 76 + 3G > T 908 + 1delG 2178 + 1G > T 3057-2A > G Q159Q 77-1G > C 908 + 1G > T 2179-2A > G 3213 + 1delG Q361Q 99-1G > T 908 + 1G > A 2343 + 1G > T 3213 + 4A > G 150 + 3A > C 1435-13 -8del 2343 + 2T > C 3213 + 5G > A 390-1G > A 2012-8T > G 2611-2A > T 611 + 1G > A 2178 + 1G > A R1001R Deletions/insertions/frame shifts Q101Dfs8X L380Wfs18X G648Vfs5X Q1058Hfs38X F959Hfs1X T127Hfs6X A382 A388del K700Sfs12X I1061Vfs34X F959Gfs48X N199Ifs14X P456Pfs24X T919del L1165del L232Cfs9X H484Rfs5X K930Efs92X A1192Efs50X R303Sfs17X I528Sfs21X K930Efs79X T1256Tfs40X V368Rfs27X I610Qfs45X K969 K972del Synonymous variants without disease association R33R F90F L232L I416I G557G I876I A1028A K1145K D36D I134I Y269Y G418G V597V G937G K1070K R52R S136S Q312Q F427F A804A Y981Y T1086T D58D V195V G319G E395E A535A G817G G1004G A1110A The overview shows ࣈ 290 known variants of BSEP on the protein level, except splice site mutations, which are shown on cDNA level. Login to comment

PMID: 24969679 [PubMed] Hu G et al: "Diagnosis of ABCB11 gene mutations in children with intrahepatic cholestasis using high resolution melting analysis and direct sequencing."

No. Sentence Comment

7 A total of 14 types of mutations/polymorphisms were identified in 20 patients from mainland China, including six missense mutations (p.Y337H, p.Y472C, p.R696W, p.Q931P, p.D1131V and p.H1198R), one nonsense mutation (p.R928X) and seven SNPs (p.D36D/rs3815675, p.F90F/rs4148777, p.Y269Y/rs2287616, p.I416I/rs183390670, p.V444A/rs2287622, p.A865V/rs118109635 and p.A1028A/rs497692). Login to comment
112 Results MutationsandSNPsdetectedinpatients.Amongthe20 patients with cholestasis, 14 types of variants were detected, including seven mutations in the coding region (p.Y337H, p.Y472C, p.R696W, p.R928X, p.Q931P, p.D1131V and p.H1198R) and seven SNPs (p.D36D/rs3815675, p.F90F/rs4148777, p.Y269Y/rs2287616, p.I416I/rs183390670, p.V444A/rs2287622, p.A865V/rs118109635 and p.A1028A/rs497692). Login to comment
118 Amino acid Carrier rate Variant Exon change RefSNP Patients and status in control (%) c.108T>C 4 D36D rs3815675 Heterozygous: P7, P11, P16 - c.270T>C 5 F90F rs4148777 Heterozygous: P6, P13 - c.807T>C 9 Y269Y rs2287616 Heterozygous: P7, P11, P16 - c.1009T>C 10 Y337H - Heterozygous: P5 0 c.1248C>A 12 I416I rs183390670 Heterozygous: P13 - c.1331T>C 13 V444A rs2287622 Heterozygous: P1, P5, P12, P16, P17, P19 94.5 Homozygous: P2, P3, P4, P6, P7, P8, P9, P10, P11, P14, P15, P18, P20 c.1415A>G 13 Y472C - Heterozygous: P3 0 c.2086C>T 18 R696W - Heterozygous: P11 0 c.2594C>T 21 A865V rs118109635 Heterozygous: P7, P17 - c.2782C>T 22 R928X - Heterozygous: P1 0 c.2792A>C 22 Q931P - Heterozygous: P4 0 c.3084A>G 24 A1028A rs497692 Heterozygous: P1, P8, P12, P13, P15, P16, P17, P20 90.5 Homozygous: P2, P3, P4, P5, P6, P7, P9, P10, P14, P18, P19 c.3392A>T 25 D1131V - Heterozygous: P3 0 c.3593A>G 26 H1198R - Heterozygous: P1 0 RefSNP refers to the reference SNP in the Single Nucleotide Polymorphism Database of NCBI. Login to comment
122 The results based on comprehensive evaluation of SIFT, PolyPhen-2, SNPs&GO and evolution conservation indicated that p.Y337H, p.Y472C, p.R696W, p.D1131V and p.H1198R were likely damaging, p.Q931P and p.A865V were possibly damaging and p.V444A was predicted to be benign. Login to comment
141 Variant SIFT PolyPhen-2 SNPs&GO EC/EN c.1009T>C (Y337H) 0.01 0.996 Disease EC c.1331T>C (V444A) 0.34 0.001 Neutral EC c.1415A>G (Y472C) 0 1.000 Disease EC c.2086C>T (R696W) 0.02 0.999 Disease EC c.2594C>T (A865V) 0.07 0.880 Disease EC c.2792A>C (Q931P) 0.02 0.178 Disease EN c.3392A>T (D1131V) 0 1.000 Disease EC c.3593A>G (H1198R) 0 1.000 Disease EC SIFT, Sorting Intolerant From Tolerant (mutation of residues with SIFT scores <0.05 are predicted to be deleterious); PolyPhen-2, Polymorphism Phenotyping version 2 (a score <0.2 denotes benign variants, between 0.2 and 0.85 is possibly damaging and >0.85 is highly likely damaging); SNPs&GO, a web tool to predict function of SNPs with a result of neutral or disease-related variants for human; EC, evolutionarily conserved; EN, evolutionarily non-conserved; SNP, single nucleotide polymorphism. Table VI. Login to comment