ABCMdb

ABCB4 p.Asn510Ser

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Publications

PMID: 23022423 [PubMed] Anzivino C et al: "ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population."

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. Login to comment
69 The p.L73V, the p.T175A and the p.N510S were previously described in literature [12,24]. Login to comment
86 Sequence analysis showed a heterozygous missense mutation in exon 13 localized at codon 510 (p.N510S) of the MDR3 protein. Login to comment
87 The PSIC score reports the p.N510S mutation as probably damaging for the protein function. Login to comment
101 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. Login to comment
127 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). Login to comment
138 The missense variant p.N510S was found for the first time in a patients with ICP in this study. Login to comment
70 The p.L73V, the p.T175A and the p.N510S were previously described in literature [12,24]. Login to comment
88 The PSIC score reports the p.N510S mutation as probably damaging for the protein function. Login to comment
102 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. Login to comment
128 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). Login to comment
139 The missense variant p.N510S was found for the first time in a patients with ICP in this study. Login to comment

PMID: 23684896 [PubMed] Condat B et al: "Prevalence of low phospholipid-associated cholelithiasis in young female patients."

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. Login to comment
62 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. Login to comment
101 [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. Login to comment
102 [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. Login to comment

PMID: 26324191 [PubMed] Degiorgio D et al: "ABCB4 mutations in adult patients with cholestatic liver disease: impact and phenotypic expression."

No. Sentence Comment

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. Login to comment
76 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). Login to comment
81 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. Login to comment
99 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. Login to comment
140 p.(N510S) Yes ICP/IBD OLT 8a,b F PSC 34 p.(E616 K) ? Login to comment

PMID: 26410236 [PubMed] Lammert F et al: "A letter on ABCB4 from Iceland: On the highway to liver disease."

No. Sentence Comment

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). Login to comment
44 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]. Login to comment