ABCB4 p.Asn510Ser
| Predicted by SNAP2: | A: D (63%), C: D (59%), D: D (63%), E: D (66%), F: D (63%), G: D (53%), H: N (61%), I: D (71%), K: D (71%), L: D (75%), M: D (66%), P: D (75%), Q: D (59%), R: D (71%), S: D (53%), T: D (63%), V: D (71%), W: D (75%), Y: D (59%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] ABCB4 and ABCB11 mutations in intrahepatic cholest... Dig Liver Dis. 2013 Mar;45(3):226-32. doi: 10.1016/j.dld.2012.08.011. Epub 2012 Sep 27. Anzivino C, Odoardi MR, Meschiari E, Baldelli E, Facchinetti F, Neri I, Ruggiero G, Zampino R, Bertolotti M, Loria P, Carulli L
ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population.
Dig Liver Dis. 2013 Mar;45(3):226-32. doi: 10.1016/j.dld.2012.08.011. Epub 2012 Sep 27., [PMID:23022423]
Abstract [show]
BACKGROUND: Genetic alterations in the ATP-binding cassette subfamily B member 4 (ABCB4) and ATP-binding cassette subfamily B member 11 (ABCB11) have been associated to the onset of intrahepatic cholestasis of pregnancy (ICP) in predisposed women. AIMS: To identify new and/or frequent ABCB4 and ABCB11 genes variants in a cohort of Italian patients with ICP and to evaluate the possible pathogenetic role for the novel mutations identified. METHODS: DNA of 33 unrelated Italian women with obstetric cholestasis were screened for mutations in the entire coding sequence of ABCB4 and ABCB11 genes. Polymerase chain reaction and automated sequencing was performed on the 27 coding exons of both genes. RESULTS: Genotyping revealed 11 mutations, 5 of whom were novel variants: 2 localized on ABCB4 (p.I587DfsX603, p.I738LfsX744) and 3 on ABCB11 (p.V284D, p.Q558H, p.P731S). The most severe phenotypes were associated with the variants p.I587DfsX603, p.I738LfsX744 and p.V284D. Moreover, the already described mutation p.N510S found in ABCB4 seems to be strictly involved in the onset of ICP in that particular patient. CONCLUSIONS: Our data support the hypothesis of a significant involvement of ABCB4 mutations in the onset of ICP, but also confirm an important role for ABCB11 mutations in increasing the susceptibility to cholestasis of pregnancy.
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No. Sentence Comment
6 Moreover, the already described mutation p.N510S found in ABCB4 seems to be strictly involved in the onset of ICP in that particular patient.
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ABCB4 p.Asn510Ser 23022423:6:43
status: NEW69 The p.L73V, the p.T175A and the p.N510S were previously described in literature [12,24].
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ABCB4 p.Asn510Ser 23022423:69:34
status: NEW86 Sequence analysis showed a heterozygous missense mutation in exon 13 localized at codon 510 (p.N510S) of the MDR3 protein.
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ABCB4 p.Asn510Ser 23022423:86:95
status: NEW87 The PSIC score reports the p.N510S mutation as probably damaging for the protein function.
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ABCB4 p.Asn510Ser 23022423:87:29
status: NEWX
ABCB4 p.Asn510Ser 23022423:87:95
status: NEW101 Nucleotide change and effect on protein Location PSIC scores by PolyPhen-2 analysis Reference 1 c.217 C > G (p. L73V) Exon 4 0.489 [12] 2 c.523 A > G (p.T175A) Exon 6 0.774 [12] 3 c.1529 A > G (p.N510S) Exon 13 2.075 [24] 4 c.1758 1759 ins G (p.I587DfsX603) Exon 15 X This study 5 c.2211(+1) G > T (p.I738LfsX744) 5 Intron 17 X This study ABCB11 mutations 6 c.403 G > A (p.E135K) Exon 6 0.502 [26] 7 c.852 T > A (p.V284D) Exon 9 2.175 This study 8 c.1445 A > G (p.D482G) Exon 14 1.364 [26-28] 9 c.1674 G > C (p.Q558H) Exon 15 1.383 This study 10 c.2093 G > A (p.R698H) Exon 18 0.821 [12,25] 11 c.2191 C > T (p. P731S) Exon 19 0.851 This study New mutations are shown in bold.
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ABCB4 p.Asn510Ser 23022423:101:196
status: NEW127 The first novel mutation detected on the ABCB4 gene is a frameshift mutation (p.I587DfsX603) and predicts the formation of Table 3 Clinical details of patients with ABCB4 mutations. Parameters Patient 1 L73V Patient 2 T175A Patient 3 N510S Patient 4 I587DfsX603 Patient 5 I738LfsX744 Onset of pruritus 3rd trimester 3rd trimester 3rd trimester 3rd trimester 2nd trimester Parity 3 2 2 2 1 Previous ICP Yes No Yes Yes Yes Peak of AST (U/L) 82 79 133 204 43 Peak of ALT (U/L) 123 156 238 382 76 Peak of Bilirubin (mg/dL) 0.14 0.81 Nd 2.8 2.07 Peak of GGT (U/L) 6 25 Nd 67 54 Total bile acids (òe;mol/L) 28.7 41 128 Nd 114.5 Delivery Caesarean section (37w+5 )a Caesarean section (36w)a Caesarean section (39w)a Caesarean section (32w)a Caesarean section (33w+4 )a Cholelithiasis No No No Yes No UDCA therapy Yes No No No Yes AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: ॹ-glutamyl transpeptidase; Nd: not determined. a Caesarean section due to pregnancy complications related to ICP (foetal distress and/or intolerable pruritus and/or persistent elevation of AST and ALT).
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ABCB4 p.Asn510Ser 23022423:127:234
status: NEW138 The missense variant p.N510S was found for the first time in a patients with ICP in this study.
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ABCB4 p.Asn510Ser 23022423:138:23
status: NEW70 The p.L73V, the p.T175A and the p.N510S were previously described in literature [12,24].
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ABCB4 p.Asn510Ser 23022423:70:34
status: NEW88 The PSIC score reports the p.N510S mutation as probably damaging for the protein function.
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ABCB4 p.Asn510Ser 23022423:88:29
status: NEW102 Nucleotide change and effect on protein Location PSIC scores by PolyPhen-2 analysis Reference 1 c.217 C > G (p. L73V) Exon 4 0.489 [12] 2 c.523 A > G (p.T175A) Exon 6 0.774 [12] 3 c.1529 A > G (p.N510S) Exon 13 2.075 [24] 4 c.1758 1759 ins G (p.I587DfsX603) Exon 15 X This study 5 c.2211(+1) G > T (p.I738LfsX744) 5 Intron 17 X This study ABCB11 mutations 6 c.403 G > A (p.E135K) Exon 6 0.502 [26] 7 c.852 T > A (p.V284D) Exon 9 2.175 This study 8 c.1445 A > G (p.D482G) Exon 14 1.364 [26-28] 9 c.1674 G > C (p.Q558H) Exon 15 1.383 This study 10 c.2093 G > A (p.R698H) Exon 18 0.821 [12,25] 11 c.2191 C > T (p. P731S) Exon 19 0.851 This study New mutations are shown in bold.
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ABCB4 p.Asn510Ser 23022423:102:196
status: NEW128 The first novel mutation detected on the ABCB4 gene is a frameshift mutation (p.I587DfsX603) and predicts the formation of Table 3 Clinical details of patients with ABCB4 mutations. Parameters Patient 1 L73V Patient 2 T175A Patient 3 N510S Patient 4 I587DfsX603 Patient 5 I738LfsX744 Onset of pruritus 3rd trimester 3rd trimester 3rd trimester 3rd trimester 2nd trimester Parity 3 2 2 2 1 Previous ICP Yes No Yes Yes Yes Peak of AST (U/L) 82 79 133 204 43 Peak of ALT (U/L) 123 156 238 382 76 Peak of Bilirubin (mg/dL) 0.14 0.81 Nd 2.8 2.07 Peak of GGT (U/L) 6 25 Nd 67 54 Total bile acids (òe;mol/L) 28.7 41 128 Nd 114.5 Delivery Caesarean section (37w+5 )a Caesarean section (36w)a Caesarean section (39w)a Caesarean section (32w)a Caesarean section (33w+4 )a Cholelithiasis No No No Yes No UDCA therapy Yes No No No Yes AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: ॹ-glutamyl transpeptidase; Nd: not determined. a Caesarean section due to pregnancy complications related to ICP (foetal distress and/or intolerable pruritus and/or persistent elevation of AST and ALT).
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ABCB4 p.Asn510Ser 23022423:128:234
status: NEW139 The missense variant p.N510S was found for the first time in a patients with ICP in this study.
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ABCB4 p.Asn510Ser 23022423:139:23
status: NEW[hide] Prevalence of low phospholipid-associated cholelit... Dig Liver Dis. 2013 Nov;45(11):915-9. doi: 10.1016/j.dld.2013.04.002. Epub 2013 May 16. Condat B, Zanditenas D, Barbu V, Hauuy MP, Parfait B, El Naggar A, Collot V, Bonnet J, Ngo Y, Maftouh A, Dugue L, Balian C, Charlier A, Blazquez M, Rosmorduc O
Prevalence of low phospholipid-associated cholelithiasis in young female patients.
Dig Liver Dis. 2013 Nov;45(11):915-9. doi: 10.1016/j.dld.2013.04.002. Epub 2013 May 16., [PMID:23684896]
Abstract [show]
BACKGROUND AND AIMS: We evaluated the prevalence of low phospholipid-associated cholelithiasis, a specific form of cholelithiasis associated with at least 2 of the 3 following criteria: first symptoms before the age of 40; intrahepatic comet tail artefacts, sludge or microlithiasis on ultrasound imaging; and recurrence of symptoms after cholecystectomy. METHODS: We prospectively studied the cases of 60 consecutive female patients under 30 with symptomatic cholelithiasis. RESULTS: A diagnosis of low phospholipid-associated cholelithiasis was made in 14/60 patients (23%). The molecular analysis showed ABCB4 (n=4) and ABCB11 (n=4) gene mutations. Low phospholipid-associated cholelithiasis was frequently observed in non-overweight patients [13/27 (48%)], was present in most patients whose biliary symptoms occurred before the age of 18 [7/10 (70%)] and was often associated with cholangitis or acute pancreatitis [9/14 (64%), p<0.05] while "common" cholelithiasis was mainly associated with cholecystitis [16/46 (35%), p<0.05]. CONCLUSION: Nearly one quarter of the female patients under the age of 30 admitted for symptomatic cholelithiasis had low phospholipid-associated cholelithiasis; particularly if body weight was normal, the symptoms began before the age of 18 or in the presence of severe biliary complications.
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No. Sentence Comment
61 Heterozygous ABCB4 gene mutations were detected in 4 patients (29%): a point mutation in the coding region (NP 000434.1: p.Arg590Gln; p.Asn510Ser) in 2 cases, a sequence variation of a RNAn splicing site (c.3486+10 dupA) whose effect on the protein is unknown in one case and a deletion of exon 10, resulting in the absence of 38 amino acids, a region carrying the entire 6th transmembrane domain of the protein (NP 000434, p.Val336 Asn373del) in one case.
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ABCB4 p.Asn510Ser 23684896:61:136
status: NEW62 Molecular analysis of the ABCB11 gene also showed variants in 4 patients (29%): a homozygous known polymorphic mutation (NP 003733: p.Val444Ala) in three cases and a heterozygous point mutation (NP 003733: p.Val43Ile) reported as a tolerated variant by protein prediction software in one case.
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ABCB4 p.Asn510Ser 23684896:62:136
status: NEW101 [18] 1 Exon 10 c.1006-162 1119+706del p.Val336 Asn373del Absence of 6th transmembrane domain [12] 1 Exon 13 c.1529A>G HTZ p.Asn510Ser HTZ Missense; IC3 Domain; deleterious according to SIFT None 1 Exon 15 c.1769G>A HTZ p.Arg590Gln HTZ Missense IC3 Domain; deleterious according to SIFT; rs45575636 [19] Exon involved NM 003742.2 (ABCB11) NP 003733 (BSEP) Consequences Bibliography 1 Exon 4 c.127G>A HTZ p.Val43Ile HTZ Missense; N-Ter Domain; tolerated according to SIFT None 3 Exon 13 c.1331T>C HMZ p.Val444Ala HMZ Missense IC3 Domain; tolerated according to SIFT; rs2287622 [14] Table 3 Characteristics of patients with low phospholipid associated cholelithiasis with and without ABCB4 or ABCB11 mutations.
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ABCB4 p.Asn510Ser 23684896:101:124
status: NEW102 [18] 1 Exon 10 c.1006-162 1119+706del p.Val336 Asn373del Absence of 6th transmembrane domain [12] 1 Exon 13 c.1529A>G HTZ p.Asn510Ser HTZ Missense; IC3 Domain; deleterious according to SIFT None 1 Exon 15 c.1769G>A HTZ p.Arg590Gln HTZ Missense IC3 Domain; deleterious according to SIFT; rs45575636 [19] Exon involved NM 003742.2 (ABCB11) NP 003733 (BSEP) Consequences Bibliography 1 Exon 4 c.127G>A HTZ p.Val43Ile HTZ Missense; N-Ter Domain; tolerated according to SIFT None 3 Exon 13 c.1331T>C HMZ p.Val444Ala HMZ Missense IC3 Domain; tolerated according to SIFT; rs2287622 [14] Table 3 Characteristics of patients with low phospholipid associated cholelithiasis with and without ABCB4 or ABCB11 mutations.
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ABCB4 p.Asn510Ser 23684896:102:124
status: NEW[hide] ABCB4 mutations in adult patients with cholestatic... J Gastroenterol. 2015 Sep 1. Degiorgio D, Crosignani A, Colombo C, Bordo D, Zuin M, Vassallo E, Syren ML, Coviello DA, Battezzati PM
ABCB4 mutations in adult patients with cholestatic liver disease: impact and phenotypic expression.
J Gastroenterol. 2015 Sep 1., [PMID:26324191]
Abstract [show]
BACKGROUND: The ABCB4 gene encodes the MDR3 protein. Mutations of this gene cause progressive familial intrahepatic cholestasis type 3 (PFIC3) in children, but their clinical relevance in adults remains ill defined. The study of a well-characterized adult patient series may contribute to refining the genetic data regarding cholangiopathies of unknown origin. Our aim was to evaluate the impact of ABCB4 mutations on clinical expression of cholestasis in adult patients. METHODS: We consecutively evaluated 2602 subjects with hepatobiliary disease. Biochemical evidence of a chronic cholestatic profile (CCP) with elevated serum gamma-glutamyltransferase activity or diagnosis of intrahepatic cholestasis of pregnancy (ICP) and juvenile cholelithiasis (JC) were inclusion criteria. The personal/family history of additional cholestatic liver disease (PFH-CLD), which includes ICP, JC, or hormone-induced cholestasis, was investigated. Mutation screening of ABCB4 was carried out in 90 patients with idiopathic chronic cholestasis (ICC), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), ICP, and JC. RESULTS: Eighty patients had CCP. PSC and ICC patients with PFH-CLD had earlier onset of disease than those without it (p = 0.003 and p = 0.023, respectively). The mutation frequency ranged from 50 % (ICP, JC) to 17.6 % (PBC). Among CCP patients, presence or absence of PFH-CLD was associated with ABCB4 mutations in 26.8 vs 5.1 % (p = 0.013), respectively; in the subset of ICC and PSC patients, the corresponding figures were 44.4 vs 0 % (p = 0.012) and 28.6 vs 8.7 % (p = 0.173). CONCLUSIONS: Cholangiopathies attributable to highly penetrant ABCB4 mutant alleles are identifiable in a substantial proportion of adults that generally have PFH-CLD. In PSC and ICC phenotypes, patients with MDR3 deficiency have early onset of disease.
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72 CCP chronic cholestatic profile, NCCP patients without chronic cholestatic profile, PBC primary biliary cirrhosis, PSC primary sclerosing cholangitis, ICP intrahepatic cholestasis of pregnancy, JC juvenile cholelithiasis, AIH autoimmune hepatitis, OS overlap syndrome between AIH and PBC or PSC, ICC idiopathic chronic cholestasis; a with (n = 14) or without (n = 23) other cholangiopathies in the personal/family history (see ''Methods``), b with (n = 9) or without (n = 15) other cholangiopathies in the personal/family history (see ''Methods``), c with (n = 2) or without (n = 2) other cholangiopathies in the personal/family history (see ''Methods``) Table 1 Heterozygous nucleotide changes within the ABCB4 gene identified in 18 adult patients with cholangiopathies and predicted impact on MDR3 Nucleotide changea Involved regions Type of mutation Mutant protein Location on the protein Degree of conservationb Reference genotypesc c.217C[G Exon 4 Missense p.(L73V) TM1 B 7, 21 c.475C[T Exon 6 Non-sense p.(R159X) ICD1 X 8, 14 c.523A[G Exon 6 Missense p.(T175A) ICD1 B 18, 21, 8, 25, 14 c.959C[T Exon 9 Missense p.(S320F) TM5 B 18, 8, 14 c.1529A[G Exon 13 Missense p.(N510S) N-ter NBD B 14 c.1531G[A Exon 13 Missense p.(A511T) N-ter NBD A 8, 14 c.1633C[T Exon 14 Missense p.(R545C) N-ter NBD A 21 c.1769G[A Exon 15 Missense p.(R590Q) N-ter NBD A 8, 13, 14, 25 c.1846G[A Exon 15 Missense p.(E616K) N-ter NBD A This study (JN392435) c.1901G[A Exon 16 Missense p.G634E Linker region B This study (JN392436) c.2431G[C Exon 20 Missense p.(G811R) ICD4 A This study (JN392437) c.2544_2548delATCAT Exon 21 Frameshift p.(S849YfsX24) TM9 X This study (JN392438) c.2576T[G Exon 21 Missense p.(L859W) TM10 B This study (JN392439) c.2844G[C Exon 23 Missense p.(M948I) TM11 B This study (JN392440) c.3541C[T Exon 27 Non-sense p.(Q1181X) C-ter NBD X This study (JN392441) TM transmembrane domain, ICD intracellular domain, N-ter NBD N-terminal nucleotide binding domain, C-ter NBD C-terminal nucleotide binding domain a The mutations were numbered according to GenBank NM_018849 and NP_061337.
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ABCB4 p.Asn510Ser 26324191:72:1173
status: NEW76 A second group of seven mutations is ascribed to type B [p.(L73V), p.(T175A), p.(N510S), p.(G634E), p.(L859W), and p.(M948I); and p.(S320F)] (Figs. 2, 3, residues in blue).
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ABCB4 p.Asn510Ser 26324191:76:81
status: NEW81 L73V T175A S320F N510S A511T R590Q E616K R545C G634E G811R L859W M948I ...69_SGLPLMMIV_77... ...69_SGLPLMMIV_77... ...66_SGLPLMMIV_74... ...66_SGLPLMMIV_74... ...69_SGLPLMMIV_77... ...69_SGLPLMMIV_77... ...67_SGLPLMMIV_75..... ...63_AGLPLMMLV_71... ...92_LGFPIMTIL_100.. ...59_MSEPLMTVV_67... ...77_GFAMPALTI_85... ...79_ASFPIMSIL_87... ..107_LGMPLMSLV_115.. ...89_AGLPLMSIL_97... ...39_ASDTFMLSL_47... ...39_ASDTFMLSL_47... ...39_AADTYMISL_47... ...28_GIPMLIPLL_36... 171_TELNTRLTD_179... 171_TELNTRLTD_179... 168_TELNTRLTD_176... 168_TELNTRLTD_176... 171_TELNTRLTD_179... 171_TELNTRLTD_179... 169_TELNTRLTD_177... 169_GELNTRLTD_177... 180_GEVVGRMSG_188... 146_GEAASRISA_154.. 164_GEVVGRMSG_172.. 167_GEVVGRMSG_175.. 197_GEITTRITT_205.. 193_GTLATKLFD_201.. 122_GTLLSRITY_130... 122_GTLLSRITY_130... 122_GGLLSRITY_130... 118_GQVISRVIN_126... 586_VIAHRLSTV_594... 586_VIAHRLSTV_594... 583_VIAHRLSTI_591... 583_VIAHRLSTV_591... 586_VIAHRLSTI_594... 586_VIAHRLSTI_594... 584_VIAHRLSTI_592... 584_VIAHRLSTV_592... 595_VVAHRLSTV_603... 561_IVAHRLSTI_569... 579_VIAHRLTTI_587... 582_IVAHRLSTV_590... 621_VIAHRLSTI_629... 608_IIAHRLSTI_616... 534_VIAHRLSTI_542... 534_VIAHRLSTI_542... 534_VIAHRLSTI_542... 531_IVAHRLSTI_539... 316_FWYGSTLVI_324... 316_FWYGSTLVI_324... 313_FWYGSTLVI_321... 313_FWYGSTLVI_321... 316_FWYGSTLVI_324... 316_FWYGSTLVI_324... 314_FWYGSTLVI_322... 314_FWYGTTLVL_322... 325_VWYGGKMIL_333... 291_FWYGAKLVI_299... 309_LWYGSKLVL_317... 312_IWFGGKMIL_320... 342_FWEGGRLLH_350... 338_FYIGVGWVH_346... 267_LYAASFPSV_275... 267_LYAASFPSV_275... 267_LFLASVDSI_275... 263 IGVGAYLAI 271... 506_VKEANAYEFI_515... 506_VKEANAYEFI_515... 503_VKEANAYDFI_512... 503_VKEANAYDFI_512... 506_VKEANAYEFI_515... 504_VKEANAYEFI_513... 504_VKDANAYEFI_513... 504_VKEANAYDFI_513... 515_TELANASKFI_524... 481_AELANAANFI_490... 499_AYLANAARFI_508... 502_TELANAAKFI_511... 541_AKLANAYDFI_550... 528_CKMANAEKFI_537... 454_ARMAYAMDFI_463... 454_ARMAYAMDFI_463... 454_ARQAHAMEFI_463... 451_AKMANAHDFI_460... 541_IAIARALVR_549... 541_IAIARALVR_549... 538_IAIARALVR_546... 538_IAIARALVR_546... 541_IAIARALVR_549... 541_IAIARALVR_549... 539_IAIARALVR_547... 539_IAIARALVR_547... 550_IAVARAILK_558... 516_IAIARAILK_524... 534_VAIARAILK_542... 537_IAIARAILK_545... 576_IAIARAVIS_584... 563_IAIARALVR_571... 489_IAIARALLR_497... 489_IAIARALLR_497... 489_VAIARALLR_497... 486_LSIARIFLN_494... ...612_GSHSELMKK_620... ...612_GSHSELMKK_620... ...609_GSHSELMKK_617... ...609_GSHSELIKK_617... ...612_GSHGELMKK_620... ...612_GNHRELMKK_620... ...610_GSHNELMKK_618... ...610_GNHDELMKE_618... ...621_GSHSELLRD_629... ...587_GSHDELIKD_595... ...605_GTHFDLVQR_613... ...608_GSHSELLKD_616... ...647_GSHNELLDL_655... ...634_GDHRALMAQ_642... ...560_GTHNDLLEH_568... ...560_GTHSELLAQ_568... ...560_GRHADLLAQ_568... ...557_GTHRELIAK_565... 630_MQTSGSQIQ_638... 630_MQTSGSQIQ_638... 627_MQTAGSQIL_635... 627_MQTSGSQIL_635... 630_TQISGSQIQ_638... 630_MQTSGNQTQ_638... 628_MQTSGNQIQ_636... 628_MQTAGNEVE_636... 640_LQEDTKQTE_648... 620_SEVSTSRLK_628... 624_LQEMHQPPP_632... 627_LQEVNKESK_635... 666_QKLSGGEKD_674... 652_AQTFTDAVD_660... 578_MQFGQ----_582... 578_MQFGQ----_582... 578_IQFGE----_582... 575_IQNL-----_578... 807_KNSTGALST_815... 807_KNSTGALST_815... 804_KNSTGALST_812... 806_KNSTGALST_814... 804_KNSTGALST_812... 809_KNSTGALST_817... 806_KNSTGALST_814... 808_KNTTGALTT_816... 825_ENSSGAIGA_833... 797_SHSSGSLGA_805... 835_ENSSGALGA_843... 822_EHSSGAIGA_830... 891_ENTVGAITT_899... 849_QNASGKIST_857... 118_KQSTGTLLS_126... 118_KQSTGTLLS_126... 118_QESTGGLLS_126... 114_NNQVGQVIS_122... 855_QLTLLLLAV_863.... 855_QLTLLLLAV_863.... 852_QLTLLLLSV_860.... 854_QLTLLLLSV_862.... 852_QLTLLLLSV_860.... 857_QLTLLLLVV_865.... 854_QLTLLLLSV_862.... 856_QLTLLLLAI_864.... 873_QLAFIVLAM_881.... 845_KLTLTIMCP_853.... 883_QLALLVLAL_891.... 870_QLALVILVL_878.... 939_KLGLVTLST_947... 897_QMALLIIAI_905.... 166_QLSIILIVL_174.... 166_QLSIILVVL_174.... 166_QLSLVLIVV_174.... 162_KLTLAALFI_170.... 944_SQAFMYFSY_952... 944_SQAFMYFSY_952... 941_SQAFMYFSY_949... 943_SQAFMYFSY_951... 941_SQAFMYFSY_949... 946_SQAFMYFSY_954... 943_SQAFMYFSY_951... 945_TQAMMYFSY_953... 962_SFFVLFSSY_970... 940_SYLMVYLTY_948... 972_SNFVLFGSY_980... 959_SFFLLFSVY_967... 1028_AQGVTFLIN_1036.. 986_ASSVLYLLN_994... 255_IQLIASLAL_263... 255_IQLIASLAL_263... 255_IQMIASLAL_263... 251_INTVTDIGP_259... Hs_MDR3 Pt_MDR3 Mm_MDR3 Rn_MDR3 Bt_MDR3 Cf_MDR3 Md_MDR3 Hs_MDR1 At_MDR Os_MDR Sm_MDR Ptr_MDR Sp_MDR Ce_P-gly Esch-coli_Msba Salm-typh_Msba Vibrio-ch_Msba Staph-au_Sav1866 Hs_MDR3 Pt_MDR3 Mm_MDR3 Rn_MDR3 Bt_MDR3 Cf_MDR3 Md_MDR3 Hs_MDR1 At_MDR Os_MDR Sm_MDR Ptr_MDR Sp_MDR Ce_P-gly Esch-coli_Msba Salm-typh_Msba Vibrio-ch_Msba Staph-au_Sav1866 Fig. 2 Multiple sequence alignment of 18 ABC proteins concerning the amino acid sequences around the 12 ABCB4 missense mutations identified in this study.
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ABCB4 p.Asn510Ser 26324191:81:17
status: NEW99 When the 19 patients affected by PBC, AIH, or OS, in whom PFH-CLD was among the enrollment criteria, were excluded from the analysis, the S320F L859W L73V M948I N-ter T175A G811R R545C A511T N510S R590Q E616K G634E C-ter Fig. 3 Ribbon representation of the three-dimensional structure of human MDR3.
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ABCB4 p.Asn510Ser 26324191:99:191
status: NEW140 p.(N510S) Yes ICP/IBD OLT 8a,b F PSC 34 p.(E616 K) ?
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ABCB4 p.Asn510Ser 26324191:140:3
status: NEW[hide] A letter on ABCB4 from Iceland: On the highway to ... Clin Res Hepatol Gastroenterol. 2015 Dec;39(6):655-8. doi: 10.1016/j.clinre.2015.08.004. Epub 2015 Sep 26. Lammert F, Hochrath K
A letter on ABCB4 from Iceland: On the highway to liver disease.
Clin Res Hepatol Gastroenterol. 2015 Dec;39(6):655-8. doi: 10.1016/j.clinre.2015.08.004. Epub 2015 Sep 26., [PMID:26410236]
Abstract [show]
Large-scale whole-genome sequencing of the Icelandic population identified an association between several mutations of ABCB4 encoding the hepatobiliary phosphatiylcholine floppase with liver diseases and function in the general population. Whereas rare mutations of this transporter were known to cause progressive familial intrahepatic cholestasis, the genome-wide association studies in Iceland find the common ABCB4 variant c.711A>T to be a general risk factor for elevated aminotransferases and higher impact variants to be potential determinants of early-onset gallstone disease, cholestasis of pregnancy, liver cirrhosis, and hepatobiliary cancer.
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37 In total, Gudbjartsson et al. [3] identified four ABCB4 variants (p.Gly622Glu, p.Leu445GlyfsX22, p.Asn510Ser, c.711A > T) to be associated with these liver-specific traits (Table 1).
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ABCB4 p.Asn510Ser 26410236:37:99
status: NEW44 n p.G622E p.L445GfsX22 p.N510S c.711A > T MAF 0.22% 0.21% 0.16% 20.54% P /OR P /OR P /OR P /OR ALT 143.693 3.0 &#d7; 10-18 0.46 2.2 &#d7; 10-11 0.35 0.004 0.18 5.7 &#d7; 10-10 -0.04 AST 144.255 2.0 &#d7; 10-10 0.28 6.8 &#d7; 10-8 0.24 0.02 0.12 0.0006 -0.02 AP 125.496 0.0004 0.17 ॹ-GT 138.195 6.5 &#d7; 10-19 0.30 0.001 0.17 1.5 &#d7; 10-5 -0.03 Gallstones 8258 7.2 &#d7; 10-10 2.74 2.6 &#d7; 10-12 3.10 0.004 1.84 0.0002 0.91 Gallstones < 40 years 2023 1.8 &#d7; 10-9 4.97 4.0 &#d7; 10-10 5.43 0.001 0.84 ICP 688 5.0 &#d7; 10-6 7.29 3.2 &#d7; 10-5 6.35 0.002 5.10 HCC/CCA 565 0.04 3.07 0.002 4.75 Cirrhosis 263 0.007 5.52 Data from Supplementary Table 13 in [3].
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ABCB4 p.Asn510Ser 26410236:44:25
status: NEW