ABCMdb

PMID: 11452359

Lu K, Lee MH, Hazard S, Brooks-Wilson A, Hidaka H, Kojima H, Ose L, Stalenhoef AF, Mietinnen T, Bjorkhem I, Bruckert E, Pandya A, Brewer HB Jr, Salen G, Dean M, Srivastava A, Patel SB
Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively.
Am J Hum Genet. 2001 Aug;69(2):278-90. Epub 2001 Jul 9., [PubMed]

Sentences

No. Mutations Sentence Comment

134 ABCG5 p.Arg419His ABCG5 p.Arg419His ABCG5 p.Arg419His ABCG5 p.Arg419His ABCG5 p.Arg419His ABCG5 p.Arg419His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg389His ABCG5 p.Arg419Pro ABCG5 p.Arg419Pro ABCG5 p.Arg419Pro ABCG5 p.Arg419Pro ABCG5 p.Arg550Ser ABCG5 p.Arg550Ser ABCG5 p.Glu146Gln ABCG5 p.Glu146Gln ABCG8 p.Gly574Glu ABCG8 p.Gly574Glu ABCG8 p.Leu596Arg ABCG8 p.Leu596Arg ABCG8 p.Leu596Arg ABCG8 p.Leu596Arg ABCG8 p.Leu501Pro ABCG8 p.Leu501Pro ABCG8 p.Pro231Thr ABCG8 p.Pro231Thr ABCG8 p.Arg543Ser ABCG8 p.Arg263Gln ABCG8 p.Arg263Gln ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Arg184His ABCG8 p.Arg184His ABCG8 p.Arg405His ABCG8 p.Arg405His A human full- Table 2 Compilation of Mutations in ABCG5 and ABCG8 PATIENT (NATIONALITY/ETHNICITY) MUTATIONS IN ABCG5a ABCG8b 4 (U.S./white) Trp361X (1173GrA) / Arg412X (1324CrT) 9 (U.S./white) Arg543Ser (1719GrT) / Gln172X (604CrT) 56c (U.S./white) Trp361X (1173GrA) / Tyr658X (2064CrG) 60 (U.S./white) Trp361X (1173GrA) / IVS1 -2 ArG 90c (U.S./white) Trp361X (1173GrA) / Trp361X (1173GrA) 94 (U.S./white) Trp361X (1173GrA) / Arg184His (641GrA) 120 (U.S./white) Trp361X (1173GrA) / Leu501Pro (1592TrC) 125 (U.S./white) Trp361X (1173GrA) / Trp361X (1173GrA) 128 (U.S./white) Leu596Arg (1877TrG) / IVS1 -2 ArG 172 (U.S./white) Trp361X (1173GrA) / Tyr658Stop (2064CrG) 166c (U.S./white) Trp361X (1173GrA) / Arg412X (1324CrT) 32 (SA/white) Arg121X (451CrT) / Arg121X (451CrT) 98 (Dutch/white) Trp361X (1173GrA) / Gly574Glu (1811GrA) 102c,d (U.S./white) Trp361X (1173GrA) / … 84c (U.S./Amish-Mennonite) Gly574Arg (1810GrA) / Gly574Arg (1810GrA) 108c (U.S./Amish-Mennonite) Gly574Arg (1810GrA) / Gly574Arg (1810GrA) 135 (Columbian/white) Trp536X (1698GrA) / Trp536X (1698GrA) 175 (French) 1798_1800delTTC / Arg405His (1304GrA) 20 (Finnish) Trp361X (1173GrA) / Trp361X (1173GrA) 154 (Finnish) Trp361X (1173GrA) / … 116 (Norwegian) Trp361X (1173GrA) / Trp361X (1173GrA) 163 (Swedish) Trp361X (1173GrA) / Leu572Pro (1805TrC) 15 (U.S./white) 1568_1572delTCTTT / IVS1 -2 ArG 143 (SA/Asian) Arg164X (580CrT) / Arg121X (451CrT) 25 (SA/Asian) Arg243X (876CrT) / Arg243X (876CrT) 40 (Japanese) Arg419His (1396GrA) / Arg419His (1396GrA) 46 (Japanese) Arg389His (1306GrA) / Arg389His (1306GrA) 63 (Japanese) del exon 3 / del exon 3 113 (Japanese) Arg389His (1306GrA) / Arg389His (1306GrA) 132 (Japanese) Arg419His (1396GrC) / Arg550Ser (1790ArC) 140 (Japanese) Arg408X (1362CrT) / Arg408X (1362CrT) 146 (Japanese) Arg389His (1306GrA) / Arg389His (1306GrA) 157 (U.S./white) Arg419Pro (1396GrC) / Arg419Pro (1396GrC) 149 (African American) Glu146Gln (576GrC) / 026; 1c,e (German/Swiss) Trp361X / Trp361X 2c,e (U.S./Amish) Gly574Arg / Gly574Arg 3c,e (U.S./white) Trp361X / Tyr658X 5c,d (U.S./white) Trp361X / Arg412X 6c,e (U.S./white) Leu596Arg / … 7d (U.S./Hispanic) Arg412X / del547Cr191X 8c,e (New Zealand/white) Trp361X / … 4e (Chinese) Arg263Gln / Pro231Thr 9e (Chinese) Arg408X / … a GenBank accession number AF312715. Login to comment 146 ABCG5 p.Arg419His ABCG5 p.Arg389His ABCG5 p.Arg419Pro ABCG5 p.Arg550Ser ABCG5 p.Arg550Ser ABCG5 p.Glu146Gln ABCG8 p.Gly574Glu ABCG8 p.Gly574Glu ABCG8 p.Leu596Arg ABCG8 p.Leu596Arg ABCG8 p.Leu501Pro ABCG8 p.Leu501Pro ABCG8 p.Pro231Thr ABCG8 p.Pro231Thr ABCG8 p.Arg543Ser ABCG8 p.Arg543Ser ABCG8 p.Arg263Gln ABCG8 p.Arg263Gln ABCG8 p.Gly574Arg ABCG8 p.Gly574Arg ABCG8 p.Arg184His ABCG8 p.Arg184His ABCG8 p.Leu572Pro ABCG8 p.Leu572Pro ABCG8 p.Arg405His ABCG8 p.Arg405His of Alleles Frequency Restriction-Enzyme Recognition ABCG5: Glu146Gln 1 .05 Gain of AlwNI Arg243X 2 .10 Gain of AlwNI Arg389His 6 .30 Loss of BstUI Arg408X 3 .15 Loss of AvaI Arg419Pro 2 .10 Loss of BstUI Arg419His 3 .15 Loss of BstUI del exon 3 2 .10 … Arg550Ser 1 .05 … Total 20 ABCG8: Arg121X 3 .061 Gain of DdeI Arg164stop 1 .020 … Gln172X 1 .020 Gain of BfaI Arg184His 1 .020 Gain of NalIII Pro231Thr 1 .020 Loss of NlaIV Arg263Gln 1 .020 Gain of AluI Trp361X 19 .39 26; Arg405His 1 .020 … Arg412X 3 .061 Gain of DdeI Leu501Pro 1 .020 Loss of AluI Trp536X 2 .041 Gain of AhdI Arg543Ser 1 .020 … Leu572Pro 1 .020 Gain of FauI Gly574Glu 1 .020 Loss of MspI Gly574Arg 4 .082 Loss of MspI Leu596Arg 1 .020 Gain of MspI Tyr658X 2 .041 Gain of SfcI IVS1 -2ArG 3 .061 Gain of BtgI 1798_1800delTTC 1 .020 … 1568_1572delTCTTT 1 .020 … Total 49 Mutations of Sterolin-2/ABCG8 as the Cause of Sitosterolemia Information on the exon/intron boundaries was used to screen probands, including those known to be mutated for sterolin-1, and to compare them to normal controls. Login to comment 154 ABCG5 p.Arg389His Table 3 shows a compilation of the frequency of each mutation identified thus far. Surprisingly, Trp361X is the most common mutation in sterolin-2, and Arg389His is the most common mutation in sterolin-1. Login to comment 155 ABCG5 p.Arg389His Surprisingly, Trp361X is the most common mutation in sterolin-2, and Arg389His is the most common mutation in sterolin-1. Login to comment 156 ABCG8 p.Gly575Arg Of interest is a 3-bp deletion in the fourth transmembrane domain of sterolin-2, resulting in the loss of phenylalanine 570; this deletion is located next to two other missense mutations but also is adjacent to a missense polymorphism (Gly575Arg) that does not appear to be deleterious (fig. 4B). Login to comment 157 ABCG8 p.Gly575Arg Of interest is a 3-bp deletion in the fourth transmembrane domain of sterolin-2, resulting in the loss of phenylalanine 570; this deletion is located next to two other missense mutations but also is adjacent to a missense polymorphism (Gly575Arg) that does not appear to be deleterious (fig. 4B). Login to comment 169 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Ala259Val ABCG8 p.Gly575Arg ABCA1 p.Cys54Tyr ABCG8 p.Glu238Lys OF IDENTIFIED POLYMORPHISMS HARDY-WEINBERG EQUILIBRIUM?ϩ/ϩ ϩ/- -/- ABCG5: 167CrT (Pro9Pro) Gain of BstNI … … … … 1950CrG (Gln604Glu) Loss of SmlI 46 25 1 Yes ABCG8: Exon 1 141CrT (Pro17Pro) … 49 1 0 Yes Exon 1 145GrC (Asp19His) Loss of BaeI 74 3 1 No Exon 2 251GrA (Cys54Tyr) Gain of SexAI 21 23 23 No Exon 6 802GrA (Glu238Lys) … 10 1 0 Yes Exon 6 866CrT (Ala259Val) Loss of HaeIII 0 5 0 … Exon 8 1289CrA (Thr400Lys) Gain of MseI 116 53 4 Yes Exon 11 1785CrT (Ala565Ala) Loss of MnlI 20 7 1 Yes Exon 11 1813GrC (Gly575Arg) Gain of HhaI 188 6 4 No Exon 13 1984CrT (Ala632Val) Loss of StyI 107 50 13 No 5 UTR -15ArC Gain of BstEII 47 4 0 Yes 5 UTR -19TrG Loss of Tsp451 38 42 29 No 5 UTR -41CrT Loss of DdeI 7 2 4 No Intron 1 -7CrT Loss of BsmAI 21 23 4 Yes Intron 1 -21CrA Loss of MnlI 20 23 4 Yes Intron 9 -19CrT … 1 3 4 … Intron 10 IVS10 ϩ34delCC … 3 1 4 … Intron 10 -50CrT … 4 4 2 … cohort of patients with sitosterolemia. Login to comment 170 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Ala259Val ABCG8 p.Gly575Arg ABCG8 p.Glu238Lys af9;/af9; af9;/afa; afa;/afa; ABCG5: 167CrT (Pro9Pro) Gain of BstNI ߪ ߪ ߪ ߪ 1950CrG (Gln604Glu) Loss of SmlI 46 25 1 Yes ABCG8: Exon 1 141CrT (Pro17Pro) ߪ 49 1 0 Yes Exon 1 145GrC (Asp19His) Loss of BaeI 74 3 1 No Exon 2 251GrA (Cys54Tyr) Gain of SexAI 21 23 23 No Exon 6 802GrA (Glu238Lys) ߪ 10 1 0 Yes Exon 6 866CrT (Ala259Val) Loss of HaeIII 0 5 0 ߪ Exon 8 1289CrA (Thr400Lys) Gain of MseI 116 53 4 Yes Exon 11 1785CrT (Ala565Ala) Loss of MnlI 20 7 1 Yes Exon 11 1813GrC (Gly575Arg) Gain of HhaI 188 6 4 No Exon 13 1984CrT (Ala632Val) Loss of StyI 107 50 13 No 5 UTR afa;15ArC Gain of BstEII 47 4 0 Yes 5 UTR afa;19TrG Loss of Tsp451 38 42 29 No 5 UTR afa;41CrT Loss of DdeI 7 2 4 No Intron 1 afa;7CrT Loss of BsmAI 21 23 4 Yes Intron 1 afa;21CrA Loss of MnlI 20 23 4 Yes Intron 9 afa;19CrT ߪ 1 3 4 ߪ Intron 10 IVS10 af9;34delCC ߪ 3 1 4 ߪ Intron 10 afa;50CrT ߪ 4 4 2 ߪ cohort of patients with sitosterolemia. Login to comment 171 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Ala259Val ABCG8 p.Gly575Arg ABCG8 p.Glu238Lys af9;/af9; af9;/afa; afa;/afa; ABCG5: 167CrT (Pro9Pro) Gain of BstNI ߪ ߪ ߪ ߪ 1950CrG (Gln604Glu) Loss of SmlI 46 25 1 Yes ABCG8: Exon 1 141CrT (Pro17Pro) ߪ 49 1 0 Yes Exon 1 145GrC (Asp19His) Loss of BaeI 74 3 1 No Exon 2 251GrA (Cys54Tyr) Gain of SexAI 21 23 23 No Exon 6 802GrA (Glu238Lys) ߪ 10 1 0 Yes Exon 6 866CrT (Ala259Val) Loss of HaeIII 0 5 0 ߪ Exon 8 1289CrA (Thr400Lys) Gain of MseI 116 53 4 Yes Exon 11 1785CrT (Ala565Ala) Loss of MnlI 20 7 1 Yes Exon 11 1813GrC (Gly575Arg) Gain of HhaI 188 6 4 No Exon 13 1984CrT (Ala632Val) Loss of StyI 107 50 13 No 5 UTR afa;15ArC Gain of BstEII 47 4 0 Yes 5 UTR afa;19TrG Loss of Tsp451 38 42 29 No 5 UTR afa;41CrT Loss of DdeI 7 2 4 No Intron 1 afa;7CrT Loss of BsmAI 21 23 4 Yes Intron 1 afa;21CrA Loss of MnlI 20 23 4 Yes Intron 9 afa;19CrT ߪ 1 3 4 ߪ Intron 10 IVS10 af9;34delCC ߪ 3 1 4 ߪ Intron 10 afa;50CrT ߪ 4 4 2 ߪ cohort of patients with sitosterolemia. Login to comment 182 ABCG5 p.Arg389His Two mutations-Arg389His in ABCG5 and Trp361X in ABCG8-are very common. Login to comment 183 ABCG5 p.Arg389His ABCG5 p.Arg389His Arg389His is found only in the Japanese population, although we did not detect this mutation a random sample of 82 Japanese subjects. Login to comment 184 ABCG5 p.Arg389His ABCG5 p.Arg389His Arg389His is found only in the Japanese population, although we did not detect this mutation a random sample of 82 Japanese subjects. Login to comment 185 ABCG5 p.Arg389His Arg389His is found only in the Japanese population, although we did not detect this mutation a random sample of 82 Japanese subjects. Login to comment