ABCMdb

ABCG5 p.Arg389His

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Publications

PMID: 11138003 [PubMed] Lee MH et al: "Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption."

No. Sentence Comment

29 We identified five point mutations: R243X (exon 6, proband 25), R389H (exon 9, probands 46, 113 and 146), R408X (exon 9, proband 140), R419H (exon 9, probands 40 and 132) and R419P (exon 9, proband 157) (Fig. 2a). Login to comment
35 Mutations resulting in R243X, R408X, R389H and R419H/P altered cleavage sites of restriction enzymes. Login to comment
50 Additionally, the first BstUI site is altered by mutation R389H (middle right panels). Login to comment
62 letter 80 nature genetics • volume 27 • january 2001 A G G A A C T G A A T T Arg Asn stop Ile C G A Arg A G G A A C A T Tnormal proband 25 T G AG T C A G CC G G Arg Val stop Ser C G A Arg C G GG T C A G Cnormal proband 140 100 200 300 400 bp 500 M C2C2+ 146 C1+ 113 132 140 41 46 63 M 100 200 300 400 500 bp M 41 46 63 113 132 140 146 C1+ C2+ C2- M AlwNI CAGNNNCTG 1 272 normal 135 141 proband 25 bp bp Ava I CPyCGPuG normal 199 109 proband 140 166 33 109 100 200 300 400 bp 500 100 200 300 400 500 M 22 23 24 25 26 27 C1+ C2+ M bp C2- 500 22 23 M 155 157 158 159 160 C1+ C2+ C2- M 155 156 4000 C C C G T AG A CC A G Gln Asp Pro Val C G C Arg C A G G A C G T A Proband 157 Normal BstUI CGCG 112 196 probands 41, 132, 157 92 normal 112 104 probands 46, 113, 146 204 104 normal 112 10492 exon 6 R243* exon 9 R408* exon 9 R389H exon 9 R419P BstUI CGCG bp bp bp bp bp bp proband 146 C T TC T CC A TA C G Thr His Leu Leu Arg normal C T TC T CC G TA C G 1 GCTCCGGGAA AACCAC---- CTGGGGACCT T--------- -------CCT 50 wild-type 1 GCTCCGGGAA AACCACGCTG CTGGACGCCA TGTCCGGGAG GCTGGGGCGC 50 51 GGGGGGTCCT TCCTGGGGGA GGTGTATGTG AACGGCCGGG CGCTGCGCCG 100 51 GCGGGGACCT TCCTGGGGGA GGTGTATGTG AACGGCCGGG CGCTGCGCCG 100 proband wild-type proband wild-type proband 101 GGAGCAGTTC CAGGACTGCT TCTCCTACGT CCTGCAG... .......... 150101 GGAGCAGTTC CAGGACTGCT TCTCCTACGT CCTGCAG... .......... 150 M wt+mut 63 64 65 66 67 C1 C2 M 61 62 mut wt wt + mut 200bp 400bp 500bp 1 2 3 4 5 6 7 8 9 10 Table 1 • Frequency of nucleotide changes in unrelated Japanese and North Americans of European descent Nucleotide change Predicted consequences Carrier frequency Restriction endonuclease changes C167T P9P not screened gain of BstNI site ∆20 bp at 402 frameshift & truncated protein no carriers in 55 Japanese controls - C867T R243X not screened gain of AlwNI site G1306A R389H no carriers in 145 Japanese and 156 Caucasians Loss of BstUI site C1362T R408X not screened loss of AvaI site G1396A R419H no carriers in 145 Japanese and 156 Caucasians Loss of BstUI site G1396C R419P no carriers in 145 Japanese and 156 Caucasians Loss of BstUI site C1950G Q604E 36% carriers in Caucasians loss of SmlI site Mutations (R243X, R408X, and R419H/P) or polymorphism Q604E were screened in unrelated Japanese and North Americans of European descent, using the restriction assays described in Fig. 2. Login to comment

PMID: 11264985 [PubMed] Lee MH et al: "Genetic basis of sitosterolemia."

No. Sentence Comment

108 Mutations in ABCG5 and ABCG8 in sitosterolemia Patients Nationality/ethnicity ABCG5 ABCG8 4 US/Caucasian Arg412X Trp361X 9 US/Caucasian Arg543Ser Gln172X 56* US/Caucasian Tyr658X Trp361X 60 US/Caucasian Trp361X ± 90* US/Caucasian Trp361X Trp361X 94 US/Caucasian Trp361X Arg184His 120 US/Caucasian Leu501Pro Trp361X 125 US/Caucasian Trp361X Trp361X 128 US/Caucasian Leu596Arg ± 32 SA Caucasian Arg121X Arg121X 98 Dutch Caucasian Gly574Glu Trp361X 102* US/Caucasian Trp361X ± 135 Columbian/Caucasian Trp536X Trp536X 20 Finnish Trp361X Trp361X 116 Norwegian Trp36X Trp361X 84* US/Amish/Mennonite Gly574Arg Gly574Arg 108 US/Amish/Mennonite Gly574Arg Gly574Arg 25 SA/Asian Arg243X Arg243X 40 Japanese Arg419His Arg419His 46 Japanese Arg389His Arg389His 63 Japanese del Exon 3 del Exon 3 113 Japanese Arg389His Arg389His 132 Japanese Arg419His ± 140 Japanese Arg408X Arg408X 146 Japanese Arg389His Arg389His 157 US/Caucasian Arg419Pro Arg419Pro 15 US/Caucasian ± ± 143 SA/Indian Asian ± ± Arg121X Arg164X 149 African American Glu145Gln ± 1* German/Swiss Trp361X Trp361X 2* US/Amish Gly574Arg Gly574Arg 3* US/Caucasian Trp361X Tyr658X 5* US/Caucasian Trp361X Arg412X 6* US/Caucasian Leu596Arg ± 7 US/Hispanic Arg412X del547C4191X 8* NZ/Caucasian Trp361X ± 4 Chinese Arg263Gln Pro231Thr 9 Chinese Arg408X ± This is a compilation of the mutations identified in ABCG5 and ABCG8. Login to comment

PMID: 15054092 [PubMed] Graf GA et al: "Missense mutations in ABCG5 and ABCG8 disrupt heterodimerization and trafficking."

No. Sentence Comment

203 No mature G5 was present in cells expressing G5 with the R389H, R419H, or N437K mutations. Login to comment
202 No mature G5 was present in cells expressing G5 with the R389H, R419H, or N437K mutations. Login to comment

PMID: 20521169 [PubMed] Niu DM et al: "Clinical observations, molecular genetic analysis, and treatment of sitosterolemia in infants and children."

No. Sentence Comment

1 We report clinical, biochemical, and molecular genetic observations and treatment outcomes for five Chinese children from four separate families presenting with sitosterolemia in whom we identified two new (Y329X, G269R) and three known (R446X, N437K, R389H) mutations in the ABCG5 gene. Login to comment
2 The R389H mutation was found in 50% of alleles. Login to comment
23 Large peaks of serum plant sterols were identified by nuclear magnetic resonance (NMR) spectroscopy, but the exact concentrations of these sterols were unable to be Table 1 Baseline lipid profiles, liver enzymes, and blood cell counts of each study patient Patient no Normal values 1 2 3 4 5 Age at diagnosis 8 years 18 months 3 months 23 months 12 years Mutation (ABCG5) Y329X R389H R389H R389H R389H N437K R446X R446X R389H G269R Initial diagnostic data Cholesterol, mg/dl Total 125-240 427 705 402 640 343 Low-density-lipoprotein 60-150 346 565 304 519 263 High-density-lipoprotein 35-84 59 64 42 64 50 Total triglycerides, mg/dl 20-200 111 149 395a 98 98 Liver enzymes Alanine transaminase, U/l 5-45 10 13 45 15 44 Aspartate aminotransferase, U/l 15-55 19 31 100 31 37 Blood count Erythrocytes, count/µl 3.7×109 -5.3×109 3.35×109 4.25×109 3.98×109 4.49×109 4.46×109 Hemoglobin, g/dl 11.5-15.5 9.8 11.8 11 12.7 12.9 Mean corpuscular volume, fl 80-95 88.5 89.0 80.6 80.2 86 White blood cells, count/µl 4,500-17,500 7,200 6,900 6,700 11,200 5,200 Platelets, count/mm3 150×106 -350×106 211×106 289×106 506×106 566×106 293×106 After ezetimibe therapy Age at plant sterols analysis NA 5 years 3 years 3 year 13 year Duration of ezetimibe treatment NA 3 years 1 year 1 year 6 months Cholesterol, total (mg/dl) 125-240 NA 181 208 223 193 Sitosterol mg/dlb 0.216±0.220 (SD)c NA 7.10 9.17 7.07 6.14 Campesterol mg/dlb 0.309±0.165 (SD)c NA 3.79 4.78 4.04 4.22 NA not available a In the nonfasting state b Plant sterols were measured by gas chromatography/mass spectrometry, as previously described (Kwiterovich et al. 2003). Login to comment
79 Patients 2 and 3 also had compound heterozygous mutations (R389H and R446X). Login to comment
80 R389H (c.1166G>A), located in exon 9, caused an arginine to be replaced by a histidine at codon 389. Login to comment
84 Patient 4 had a homozygous mutation, R389H. Login to comment
85 Patient 5 had compound heterozygous mutations, p.R389H and p.G269R. Login to comment

PMID: 20543520 [PubMed] Tsubakio-Yamamoto K et al: "Current therapy for patients with sitosterolemia--effect of ezetimibe on plant sterol metabolism."

No. Sentence Comment

108 Location of the gene mutation and hematological/ biochemical laboratory data in case 1 (at the time of PCI) and case 2 (at the first visit) Case 1 Case 2 ABCG5 mutation WBC (/ L) RBC ( 104 / L) Hemoglobin (g/dL) Platelet ( 104 / L) AST (IU/L) ALT (IU/L) CRP (mg/dL) Total Cholesterol (mg/dL) LDL Cholesterol (mg/dL) HDL Cholesterol (mg/dL) Triglyceride (mg/dL) Sitosterol ( g/mL) Campesterol ( g/mL) Stigmasterol ( g/mL) A1756C (R550S) G1362A (R419H) 7,610 382 9.8 18.5 14 16 0.3 172 87 67 121 87.8 48.8 4.0 G1306A (R389H) C1949 (Q604E) 6,370 385 10.9 12.5 29 26 1.0 289 229 85 172 88.5 84.5 7.2 Fig.3. Login to comment

PMID: 15375183 [PubMed] Wang J et al: "Phenotypic heterogeneity of sitosterolemia."

No. Sentence Comment

115 In this ethnic group, ABCG5 exon 9 is most commonly affected, and the most common mutation is R389H. Login to comment
113 In this ethnic group, ABCG5 exon 9 is most commonly affected, and the most common mutation is R389H. Login to comment

PMID: 12359125 [PubMed] Burris TP et al: "Genetic disorders associated with ATP binding cassette cholesterol transporters."

No. Sentence Comment

112 Regulation of ABC cholesterol transporters by LXR/ RXR heterodimer One feature of ABC transporters is that they are usually feed back/forward regulated by their own sub-Table 2 Summary of mutations described in sitosterolemia Nucleotide sequence change Protein sequence change ABC transporters References 402Del Truncated protein ABCG5 [12] C867T R243X ABCG5 [12] G1306A R389H ABCG5 [12] C1362T R408X ABCG5 [11,12] G1396A R419H ABCG5 [12] G1396C R419P ABCG5 [12] 547Del P231T ABCG8 [11] A691C 191Stop ABCG8 [11] G788A R263Q ABCG8 [11] G1083A W361Stop ABCG8 [11] C1234T R412stop ABCG8 [11] G1720A G574R ABCG8 [11] T1787G L596R ABCG8 [11] C1974G Y658Stop ABCG8 [11] strates at the level of transcription. Login to comment

PMID: 21862702 [PubMed] Calandra S et al: "Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk."

No. Sentence Comment

169 A few of the mutations are over-represented in certain ethnic groups (e.g., ABCG5, R389H in Japanese, Chinese (71, 85), ABCG8, W361X in Europeans (45, 59, 81), implying founder effects, but otherwise, each mutation is confined to one or two kindred. Login to comment

PMID: 21664501 [PubMed] Keller S et al: "Increased plasma plant sterol concentrations and a heterozygous amino acid exchange in ATP binding cassette transporter ABCG5: a case report."

No. Sentence Comment

57 In addition to splicing, insertions, deletion, and complete rearrangement of the ABCG5 gene,13 mutations with an amino acid exchange resulting in sitosterolemia are published (Gln22Term [14], Glu77Term [15], Glu146Gln [16], Arg243Term [17], Gly269Arg, Tyr329Term [7], Arg389His, Arg408Term, Arg419His, Arg419Pro [17], Asn437Lys [18], Arg446Term [1], Arg550Ser [16]). Login to comment
58 Five of the 13 mutations are located in exon 9 of the ABCG5 gene (Arg389His, Arg408Term, Arg419His, Arg419Pro, Asn437Lys) corresponding to our findings regarding the amino acid exchange Arg406Gln. Login to comment

PMID: 11452359 [PubMed] Lu K et al: "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."

No. Sentence Comment

134 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) / … 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 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 … 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 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
182 Two mutations-Arg389His in ABCG5 and Trp361X in ABCG8-are very common. Login to comment
183 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 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
155 Surprisingly, Trp361X is the most common mutation in sterolin-2, and Arg389His is the most common mutation in sterolin-1. Login to comment
185 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