ABCA3 p.Leu1552Pro
| Predicted by SNAP2: | A: N (57%), C: N (72%), D: D (63%), E: N (61%), F: N (72%), G: D (59%), H: N (66%), I: N (93%), K: N (53%), M: N (93%), N: N (57%), P: D (66%), Q: N (72%), R: N (53%), S: N (61%), T: N (78%), V: N (87%), W: D (53%), Y: N (66%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] ABCA3 gene mutations in newborns with fatal surfac... N Engl J Med. 2004 Mar 25;350(13):1296-303. Shulenin S, Nogee LM, Annilo T, Wert SE, Whitsett JA, Dean M
ABCA3 gene mutations in newborns with fatal surfactant deficiency.
N Engl J Med. 2004 Mar 25;350(13):1296-303., [PMID:15044640]
Abstract [show]
BACKGROUND: Pulmonary surfactant forms a lipid-rich monolayer that coats the airways of the lung and is essential for proper inflation and function of the lung. Surfactant is produced by alveolar type II cells, stored intracellularly in organelles known as lamellar bodies, and secreted by exocytosis. The gene for ATP-binding cassette transporter A3 (ABCA3) is expressed in alveolar type II cells, and the protein is localized to lamellar bodies, suggesting that it has an important role in surfactant metabolism. METHODS: We sequenced each of the coding exons of the ABCA3 gene in blood DNA from 21 racially and ethnically diverse infants with severe neonatal surfactant deficiency for which the etiologic process was unknown. Lung tissue from four patients was examined by high-resolution light and electron microscopy. RESULTS: Nonsense and frameshift mutations, as well as mutations in highly conserved residues and in splice sites of the ABCA3 gene were identified in 16 of the 21 patients (76 percent). In five consanguineous families with mutations, each pair of siblings was homozygous for the same mutation and each mutation was found in only one family. Markedly abnormal lamellar bodies were observed by ultrastructural examination of lung tissue from four patients with different ABCA3 mutations, including nonsense, splice-site, and missense mutations. CONCLUSIONS: Mutation of the ABCA3 gene causes fatal surfactant deficiency in newborns. ABCA3 is critical for the proper formation of lamellar bodies and surfactant function and may also be important for lung function in other pulmonary diseases. Since it is closely related to ABCA1 and ABCA4, proteins that transport phospholipids in macrophages and photoreceptor cells, it may have a role in surfactant phospholipid metabolism.
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No. Sentence Comment
85 The sequences of the puffer fish and the zebra fish are not complete, resulting in some gaps in this information in the case of L982P, G1221S, L1552P, L1553P, and L1580P.
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ABCA3 p.Leu1552Pro 15044640:85:143
status: NEW84 The sequences of the puffer fish and the zebra fish are not complete, resulting in some gaps in this information in the case of L982P, G1221S, L1552P, L1553P, and L1580P.
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ABCA3 p.Leu1552Pro 15044640:84:143
status: NEW[hide] Haplotype analysis of ABCA3: association with resp... Ann Med. 2008;40(1):56-65. Karjalainen MK, Haataja R, Hallman M
Haplotype analysis of ABCA3: association with respiratory distress in very premature infants.
Ann Med. 2008;40(1):56-65., [PMID:18246475]
Abstract [show]
BACKGROUND: Adenosine triphosphate (ATP)-binding cassette transporter A3 (ABCA3) gene mutations cause fatal respiratory failure in term infants, but common ABCA3 polymorphisms have remained uncharacterized at the population level. AIM: To define a subset of tagging single-nucleotide polymorphisms (tSNPs) which capture most of the variation within the ABCA3 gene, and to assess ABCA3 as a novel candidate gene for susceptibility to respiratory distress syndrome (RDS) in preterm infants. METHODS: Based on an initial screen, nine tSNPs were selected. These 9 tSNPs and a length variation, representing > 90% of haplotypic variation of the gene, and 5 nonsynonymous coding SNPs were genotyped in 267 preterm infants. SNP rs13332514 was genotyped in an additional 48 infants. RESULTS: The fourth common haplotype was overrepresented in very premature infants with RDS, being accounted for by SNP rs13332514 (F353F), with an increased minor allele frequency in RDS. Furthermore, rs13332514 associated significantly with chronic lung disease defined as a requirement for supplemental O2 at 28 postnatal days in very premature infants. CONCLUSIONS: The results are suggestive of an association of a synonymous SNP in the ABCA3 gene with a prolonged course of respiratory distress syndrome in very premature infants and serve as a reference for further population-based studies of ABCA3.
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No. Sentence Comment
90 SNP rs149532 (corresponding to residue S1372S) was rare (MAF50.02) in our population, and it was thus excluded from further analysis, together with the nonpolymorphic cSNPs (rs28936412, 875AwT, rs13332760, rs28936690, and rs28936691, corresponding to residues L101P, E292V, V839F, L1552P, and Q1591P, respectively).
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ABCA3 p.Leu1552Pro 18246475:90:281
status: NEW94 SNP No. or position a Alleles (major/minor) Position b Location Affected residue Minor allele frequency tSNPs c Best pairwise r2 value and the corresponding tSNP d rs28936412 T/C 2316029 Exon 5 L101P 0 - 320-17GwA G/A 2314550 Intron 5 0.055 tSNP1 875AwT A/T 2307765 Exon 9 E292V 0 - rs13332547 C/T 2307425 Intron 9 0.093 tSNP2, r2 51 rs13332514 C/T 2307337 Exon 10 F353F 0.093 tSNP2 rs323069 G/C 2304052 Intron 10 0.271 tSNP3 rs323073 C/T 2298761 Intron 10 0.283 tSNP3, r2 50.831 rs323074 G/A 2298314 Intron 11 0.201 tSNP5, r2 50.848 rs323033 A/G 2296546 Intron 11 0.259 tSNP4 rs323040 G/A 2290527 Intron 12 0.168 tSNP5 rs170447 A/G 2289372 Intron 14 0.396 tSNP6, r2 50.832 rs2240523 T/C 2288658 Intron 14 0.381 tSNP6, r2 50.849 rs17183533 A/G 2285389 Intron 18 0.420 tSNP7, r2 50.986 rs13332760 G/T 2279621 Exon 20 V839F 0 - rs313909 C/T 2277994 Intron 21 0.373 tSNP6 rs2014467 A/G 2276395 Intron 22 0.424 tSNP7 rs2238464 G/A 2272578 Intron 26 0.420 tSNP8 rs149532 T/C 2271431 Exon 27 S1372S 0.020 - rs150926 G/C 2270170 Intron 28 0.372 tSNP6, r2 50.975 rs150928 C/T 2268651 Intron 29 0.226 tSNP9 rs28936690 T/C 2268353 Exon 30 L1552P 0 - rs28936691 A/C 2268018 Exon 31 Q1591P 0 - a rs numbers are shown for SNPs with entries in dbSNP. SNPs without entries in dbSNP are numbered from start codon as advised in (34).
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ABCA3 p.Leu1552Pro 18246475:94:1129
status: NEW129 None of the five nonsynonymous cSNPs (rs28936412, 875AwT, rs13332760, rs28936690, and rs28936691, corresponding to residues L101P, E292V, V839F, L1552P, and Q1591P, respectively) were detected in any individuals.
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ABCA3 p.Leu1552Pro 18246475:129:145
status: NEW213 In our study population, however, neither these nor the two other nonsynonymous cSNPs (corresponding to V839F and L1552P) listed in dbSNP were polymorphic, suggesting that they represent mutations rather than common polymorphisms.
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ABCA3 p.Leu1552Pro 18246475:213:114
status: NEW