ABCMdb

ABCD4 p.Tyr319Cys

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Publications

PMID: 22922874 [PubMed] Coelho D et al: "Mutations in ABCD4 cause a new inborn error of vitamin B(12) metabolism."

No. Sentence Comment

40 Subject 1 carried a missense mutation, c.956A>G (p.Tyr319Cys) (NM_005050.3), predicted to be probably damaging with a score of 0.984 using the PolyPhen-2 program5, and a dinucleotide insertion, c.1746_1747insCT (p.Glu583Leufs*9), resulting in a frameshift and the introduction of a premature stop codon leading to removal of 14 amino acids from the C terminus. Login to comment
71 Among the four mutations detected in our affected subjects, two (encoding p.Asp143_Ser181del and p.Tyr319Cys) occur in the predicted transmembrane domain, whereas the other two (encoding p.Gly443_ Ser485del and p.Glu583Leufs*9) are located in the predicted NBD11. Login to comment
82 The position of the p.Tyr319Cys and p.Glu583Leufs*9 alterations (detected in subject 1) are represented with a red dot, and the polypeptide fragments deleted in the p.Asp143_Ser181del and p.Gly443_Ser485del protein products (detected in subject 2) are highlighted in red. Login to comment
86 Mutant alleles encoding changes to highly conserved amino-acid residues known to be involved in ATPase activity, for example, p.Lys427Leu in the Walker A site, p.Asp548Asn in the Walker B site and p.Glu549Gln in the putative catalytic domain of ABCD4, were transfected transiently into immortalized fibroblasts from subject 1 by electroporation and were assayed for rescue of AdoCbl and MeCbl synthesis. Login to comment
89 a Intralysosomal Membrane Cytosolic H2N 37 54 81 98 Asp143 Gly443 p.Gly443_Ser485del Ser485 536 421 ATP binding (Walker B) COOH 606 p.Glu583Leufs*9 p.Tyr319Cys 35 30 ATP binding (Walker A) p.Asp143_Ser181del 160 177 Ser181 206 189 293 313 330276 b 25 20 15 10 5 0 PercentageoftotalCbl AdoCbI MeCbI Vectoronly ABC D 4-p.Lys427Leu ABC D 4-p.G lu549G ln ABC D 4-p.Asp548Asn ABC D 4-w t Figure 5 Subcellular localization of ABCD4 detected by fluorescence and confocal microscopy. Login to comment
75 Among the four mutations detected in our affected subjects, two (encoding p.Asp143_Ser181del and p.Tyr319Cys) occur in the predicted transmembrane domain, whereas the other two (encoding p.Gly443_ Ser485del and p.Glu583Leufs*9) are located in the predicted NBD11. Login to comment
93 a Intralysosomal Membrane Cytosolic H2N 37 54 81 98 Asp143 Gly443 p.Gly443_Ser485del Ser485 536 421 ATP binding (Walker B) COOH 606 p.Glu583Leufs*9 p.Tyr319Cys 35 30 ATP binding (Walker A) p.Asp143_Ser181del 160 177 Ser181 206 189 293 313 330 276 b 25 20 15 10 5 0 Percentage of total Cbl AdoCbI MeCbI V e c t o r o n l y A B C D 4 - p . Login to comment