ABCMdb

ABCC6 p.Ala950Val

LOVD-ABCC6:	p.Ala950Thr D
Predicted by SNAP2:	C: D (80%), D: D (95%), E: D (95%), F: D (95%), G: D (91%), H: D (95%), I: D (66%), K: D (95%), L: D (91%), M: D (91%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: D (66%), T: D (71%), V: D (75%), W: D (95%), Y: D (95%),
Predicted by PROVEAN:	C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: D, Y: N,

[switch to compact view]
Comments [show]

None has been submitted yet.

Publications
[hide] Novel mutations of ABCC6 gene in Japanese patients... Biochem Biophys Res Commun. 2009 Mar 13;380(3):548-53. Epub 2009 Jan 25. Sato N, Nakayama T, Mizutani Y, Yuzawa M
Novel mutations of ABCC6 gene in Japanese patients with Angioid streaks.
Biochem Biophys Res Commun. 2009 Mar 13;380(3):548-53. Epub 2009 Jan 25., 2009-03-13 [PMID:19284998]

Abstract [show]
Angioid streaks (AS) are eye abnormalities caused by breaks in Bruch's membrane. The condition is often associated with pseudoxanthoma elasticum (PXE). The ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6) is reported to be the causal gene for PXE, although there have been no reports on whether the ABCC6 gene is the causal gene for AS. The aims of this study are to isolate the causal mutations for AS using a haplotype-based case-control study. We genotyped 54 Japanese AS patients and 150 controls for 5 single-nucleotide polymorphisms (SNPs). A simple association study using each SNP and a haplotype-based case-control study were performed. Twelve patients with special haplotypes for AS were selected, and were then subjected to gene sequencing. Six variants were successfully identified as causal mutations for AS (p.R419Q, p.E422K, c.2542delG, Del_Exon23, c.3774-3775insC and p.E1427K), and 4 of these were novel. This method can be applied to both identifying susceptibility variants of multifactorial diseases and isolating mutations in single-gene diseases.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
84 We identified 8 nonsynonymous variants and a deletion variant in the exon regions; p.R419Q (Exon10), p.S587C (exon13), p.V614A (Exon14), p.H632Q (Exon15), c.2542delG (Exon19), p.A950V (Exon22), p.R1268Q (Exon27) and p.E1427K (Exon30). Login to comment
106 The heterozygous p.E1427K and p.V614A or p.H632Q or p.R1268Q were found in a subject with the heterozygous GTAA/ATGG diplotype. The heterozygous c.2542delG and p.V614A or p.H632Q were found in a subject with the heterozygous GTAA/ACAA diplotype. The heterozygous p.S587C was found in a subject with the heterozygous GTGA/GCGA diplotype, and the heterozygous p.A950V was found in a subject with the heterozygous GTAA/GCAA diplotype. Login to comment
109 Consequently, p.S587C (exon13), p.V614A (Exon14), p.H632Q (Exon15), p.A950V (Exon22) and p.R1268Q (Exon27) were excluded from among the disease-causing mutations because they were seen in the control group. Login to comment
114 of patients PXE Non-PXE Unknown GTGG/GTGG 8 p.R419Q/p.R419Q 5 3 1 1 p.R419Q/À 1 0 0 1 À/À 2 0 0 2 GTGG/GTGA 8 p.R419Q/À 2 2 0 0 À/À 6 4 0 2 ATGA/ATGA 8 c.2542delG/c.2542delG 7 4 2 1 c.2542delG/À 1 1 0 0 GTGG/ATGA 5 c.2542delG/À 4 3 0 1 À/À 1 1 0 0 GTGA/GTGA 4 Del_Exon23/Del_Exon23 2 1 0 1 À/À 2 2 0 0 GTAA/GTAA 3 À/À 3 3 0 0 ATGA/GTGA 3 c.2542delG/À 2 2 0 0 À/À 1 0 0 1 ATGA/GTAA 3 p.E422K/c.2542delG 1 1 0 0 c.2542delG/À 1 1 0 0 À/À 1 0 0 1 GTGA/GTAA 2 À/À 2 1 1 0 GTAA/ACAA 2 c.2542delG/À 2 2 0 0 GTGG/GCGA 1 À/À 1 1 0 0 GTGG/ATGG 1 p.R419Q/p.R419Q 1 0 0 1 GTGA/GCGA 1 p.S587C/À 1 0 1 0 GTGA/GCAA 1 À/À 1 1 0 0 GTGA/ACAA 1 c.2542delG/c.3774-3775insC 1 0 1 0 GTAA/GCAA 1 p.A950V/À 1 0 1 0 GTAA/ATGG 1 p.E1427K/À 1 0 0 1 ATGA/ATGG 1 c.2542delG/À 1 1 0 0 For ABCC6 proteins, the designations for the mutations refer to the position of the amino acid substitution, where amino acid terminus. Nonsynonymous variants were shown by the amino acid numbers started by the strat codon methionine. The cDNA base numbers refer to the nucleotide in the cDNA, where nucleotide 1 is the A of the first ATG. Exon22 Exon23 Exon24 Wile Type 32nortnI22nortnI Exon22 Exon24 Mutation Type Intron23Intron22 Breakpoint (3901bp Deletion) Fig. 3. Login to comment
119 The most common alleles were c.2542delG (25.0%), p.R419Q (13.9%), Del_Exon23 (3.7%), followed by c.3774-3775insC, p.E422K, p.S587C, p.A950V and p.E1427K (all 0.93%). Login to comment
121 There were 17 patients with only 1 allele, 11 patients with c.2542delG/À, 3 with p.R419Q/À, 1 with p.S587C/À, 1 with p.A950V/À and 1 with p.E1427K/À. Login to comment
123 The p.N428S/À, p.A950V/À, p.V438M/À, c.2542delG/À, p.S587C/À and p.N428S/À mutations were also seen in the control group. Login to comment
157 Exon Mutation AS Control Decision Wild/Wild Wild/Mut Mut/Mut Wild/Wild Wild/Mut Mut/Mut Undetermine 10 c.1256G>A (p.R419Q) 45 3 6 150 0 0 0 * 10 c.1264G>A (p.E422K) 53 1 0 150 0 0 0 * 10 c.1283A>G (p.N428S) 54 0 0 148 2 0 0 # 10 c.1312G>A (p.V438M) 54 0 0 149 1 0 0 # 13 c.1760C>G (p.S587C) 53 1 0 149 1 0 0 # 14 c.1841T>C (p.V614A) 40 12 2 89 56 5 0 $ 15 c.1896C>A (p.H632Q) 30 15 9 90 55 5 0 $ 19 c.2542delG 34 13 7 149 1 0 0 * 22 c.2849C>T (p.A950V) 53 1 0 149 1 0 0 # 23 Del_Exon23 52 0 2 150 0 0 0 * 27 c.3803G>A (p.R1268Q) 29 16 9 105 42 3 0 $ 27 c.3774-3775insertC 53 1 0 147 0 0 3 * 30 c.4279G>A (p.E1427K) 53 1 0 150 0 0 0 * For ABCC6 proteins, the designations for the mutations refer to the position of the amino acid substitution, where amino acid terminus. Nonsynonymous variants were shown by the amino acid numbers started by the strat codon methionine. The cDNA base numbers refer to the nucleotide in the cDNA, where nucleotide 1 is the A of the first ATG. * Causal mutation definitely. Login to comment