ABCB4 p.Tyr467Phe
| Predicted by SNAP2: | A: D (63%), C: N (66%), D: D (71%), E: D (71%), F: N (66%), G: D (66%), H: N (72%), I: D (63%), K: D (59%), L: D (66%), M: D (59%), N: D (66%), P: D (80%), Q: D (66%), R: D (71%), S: D (59%), T: D (63%), V: D (59%), W: N (93%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: N, |
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[hide] ABCB4 sequence variations in young adults with cho... Liver Int. 2009 May;29(5):743-7. Epub 2008 Oct 24. Nakken KE, Labori KJ, Rodningen OK, Nakken S, Berge KE, Eiklid K, Raeder MG
ABCB4 sequence variations in young adults with cholesterol gallstone disease.
Liver Int. 2009 May;29(5):743-7. Epub 2008 Oct 24., [PMID:19018976]
Abstract [show]
BACKGROUND AND AIMS: Mutations in the gene encoding the ABCB4 [adenosine triphosphate (ATP)-binding cassette, sub-family B (MDR/TAP), member 4] transporter lower phosphatidylcholine output into bile and contribute to cholesterol gallstone formation by decreasing the solubility of cholesterol in bile. Mutations in ABCB4 have been identified in patients with low phospholipid-associated cholelithiasis. The aim of the present study was to determine the types and frequencies of ABCB4 mutations in cholecystectomized patients aged <40 years. PATIENTS AND METHODS: Hundred and four patients (mean age 30.6 years, range 12-39) were included in the study and the ABCB4 gene was sequenced. The frequency of missense mutations found in the patient material was measured in 95 healthy controls. The potential functional implications of the ABCB4 missense variations were assessed by computerized analysis (BLOSUM62 and Grantham substitution matrices, polymorphism phenotyping and sorting intolerant from tolerant). RESULTS: One patient was heterozygous for a frameshift mutation (c.1399_1400ins10/p.Y467F fsX25). Another patient was heterozygous for a nonsense mutation (c.3136C>T/p.R1046X). These two mutations are considered detrimental to ABCB4 protein function. In addition, six missense mutations were found in the ABCB4 gene, and three of these were only present in patients. CONCLUSION: In our study, <2% of young gallstone patients were found to be heterozygous for detrimental ABCB4 mutations. The functional implication of several missense mutations remains to be clarified. Thus, mutations in the ABCB4 gene are a rare cause of gallstone disease.
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No. Sentence Comment
7 Results: One patient was heterozygous for a frameshift mutation (c.1399_1400ins10/p.Y467F fsX25).
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ABCB4 p.Tyr467Phe 19018976:7:84
status: NEW59 Another patient was heterozygous for a 10 base pair insertion in exon (13) (c.1399_1400 ins10), resulting in a frameshift, followed by a premature stop codon (p.Y467F fsX25).
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ABCB4 p.Tyr467Phe 19018976:59:161
status: NEW86 Four of the eight identified ABCB4 gene variants have not been reported before (p.M113L, p.Q1106H, p.Y467F fsX25 and p.R1046X).
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ABCB4 p.Tyr467Phe 19018976:86:101
status: NEW88 Table 1. Summary of patient characteristics having ABCB4 gene variations with possible effects on the ABCB4 protein and the occurrence of these variations in healthy controls Patient (ID) (n = 104) Gender/ethnicity Age Indication for surgery Gallstone Location Nucleotide change Peptide change Status Controls (n = 95) 1-16 Female Exon 16 c.1954A 4 G p.R652G 9 17-22 Female/Norwegian 21 Choledocholithiasis Multiple, 5 mm Exon 6 c.523A 4 G p.T175A heterozygous 3 Female/Iraq 25 Cholecystolithiasis Multiple, 5-10 mm Female/Norwegian 28 Cholecystolithiasis Two, 15 mm Female/African 31 Cholecystitis Multiple, 5 mm1solitary, 20 mm Female/Norwegian 32 Cholecystolithiasis Multiple, 5 mm Female/Norwegian 34 Cholecystolithiasis Multiple, 5-10 mm 23 Female/Norwegian 32 Cholecystolithiasis Two, 20 mm Exon 14 c.1584G 4 C p.E528D heterozygous 0 24-25 Female/Norwegian 23 Cholecystolithiasis Multiple, 5 mm Exon 15 c.1769G 4 A p.R590Q heterozygous 1 Female/Norwegian 37 Cholecystolithiasis Multiple, o 5 mm 26 Female/Norwegian 40 Cholecystitis Solitary, 30 mm Exon 25 c.3136C 4 T p.R1046X heterozygous - 27 Female/Pakistani 30 Cholecystolithiasis Three, 10 mm Exon 13 c.1399_1400 ins10 p.Y467F fsX25 heterozygous - 28 Ã Female/Pakistani 32 Cholecystolithiasis Multiple, o 5 mm Exon 5 c.337A 4 G p.M113L heterozygous 0 Exon 26 c.3318G 4 C p.Q1106H 0 The variation p.R652G, considered to be without functional significance for the ABCB4 product, is shown without patient characteristics (16 patients).
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ABCB4 p.Tyr467Phe 19018976:88:1182
status: NEW99 The nonsense mutation c.3136C 4 T resulting in a premature stop codon p.R1046X and the insertion c.1399_1400 ins10 resulting in frameshift, followed by a premature stop codon (p.Y467F fsX25), are the two mutations that most probably affected the function of the ABCB4 protein in our patient material.
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ABCB4 p.Tyr467Phe 19018976:99:178
status: NEW136 The mutations found were c.3136C 4 T/p.R1046X and c.1399_1400ins10/p.Y467F fsX25.
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ABCB4 p.Tyr467Phe 19018976:136:69
status: NEW