ABCA12 p.Arg1514His
ClinVar: |
c.4541G>A
,
p.Arg1514His
D
, Pathogenic
|
Predicted by SNAP2: | A: D (85%), C: D (91%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (91%), I: D (91%), K: D (95%), L: D (95%), M: D (91%), N: D (95%), P: D (95%), Q: D (91%), S: D (91%), T: D (91%), V: D (95%), W: D (95%), Y: D (91%), |
Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Mutations in the transporter ABCA12 are associated... Hum Mol Genet. 2003 Sep 15;12(18):2369-78. Epub 2003 Jul 15. Lefevre C, Audebert S, Jobard F, Bouadjar B, Lakhdar H, Boughdene-Stambouli O, Blanchet-Bardon C, Heilig R, Foglio M, Weissenbach J, Lathrop M, Prud'homme JF, Fischer J
Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2.
Hum Mol Genet. 2003 Sep 15;12(18):2369-78. Epub 2003 Jul 15., [PMID:12915478]
Abstract [show]
Lamellar ichthyosis type 2 (LI2) is a rare autosomal recessive skin disorder for which a gene has been localized on chromosome 2q33-35. We report the identification of five missense mutations in the ABCA12 gene in nine families from Africa affected by LI2. The mutations were homozygous in eight consanguineous families and heterozygous in one non-consanguineous family. Four of these mutations are localized in the first ATP-binding domain (nucleotide-binding fold), which is highly conserved in all ABC proteins. The ABCA12 protein belongs to a superfamily of membrane proteins that translocate a variety of substrates across extra- and intracellular membranes. ABCA transporters have been implicated in several autosomal recessive disorders, notably of lipid metabolism. By analogy with ABCA3, a lamellar body membrane protein in lung alveolar type II cells, ABCA12 could function in cellular lipid trafficking in keratinocytes.
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No. Sentence Comment
64 Origin of families and mutations Family Number of patients Degree of consanguinity Origin Mutation Effect Exon number A 3 1st Morocco 4142G!A G1381E 28 C 1 1st Morocco 4139A!G N1380S 28 D 1 1st Morocco 4139A!G N1380S 28 E 1 1st Morocco 4139A!G N1380S 28 F 3 1st Algeria 4951G!A G1651S 32 G 3 No Algeria 4139A!G N1380S 28 4851G!A G1651S 32 H 1 1st Mali 4541G!A R1514H 30 I 1 1st Algeria 4139A!G N1380S 28 J 1 1st Algeria 4615G!A E1539K 31 neonate mouse skin (AK028781, AK029031).
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ABCA12 p.Arg1514His 12915478:64:360
status: NEW75 All of the mutations were missense mutations and were found in the region of the protein encoded by exons 28-32: 4139A!G (N1380S) and 4142G!A (G1381E) in exon 28, 4541G!A (R1514H) in exon 30, 4615G!A (E1539K) in exon 31 and 4951G!A (G1651S) in exon 32.
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ABCA12 p.Arg1514His 12915478:75:172
status: NEW88 Four of the mutations (N1380S, G1381E, R1514H, E1539K) were situated in the first highly conserved ATP binding domain of the protein (Fig. 4).
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ABCA12 p.Arg1514His 12915478:88:39
status: NEW[hide] Novel adenosine triphosphate (ATP)-binding cassett... Br J Dermatol. 2012 Jan;166(1):218-21. doi: 10.1111/j.1365-2133.2011.10516.x. Epub 2011 Sep 29. Fukuda S, Hamada T, Ishii N, Sakaguchi S, Sakai K, Akiyama M, Shimizu H, Masuda K, Izu K, Teye K, Tsuruta D, Karashima T, Nakama T, Yasumoto S, Hashimoto T
Novel adenosine triphosphate (ATP)-binding cassette, subfamily A, member 12 (ABCA12) mutations associated with congenital ichthyosiform erythroderma.
Br J Dermatol. 2012 Jan;166(1):218-21. doi: 10.1111/j.1365-2133.2011.10516.x. Epub 2011 Sep 29., [PMID:21729033]
Abstract [show]
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No. Sentence Comment
63 Only three of 17 mutations (p.Asn1380Ser, p.Ile1494Thr and p.Arg1514His) were located in the first nucleotide-binding folds.
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ABCA12 p.Arg1514His 21729033:63:61
status: NEW[hide] ABCA12 mutations and autosomal recessive congenita... Hum Mutat. 2010 Oct;31(10):1090-6. Akiyama M
ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts.
Hum Mutat. 2010 Oct;31(10):1090-6., [PMID:20672373]
Abstract [show]
Mutations in ABCA12 have been described in autosomal recessive congenital ichthyoses (ARCI) including harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). HI shows the most severe phenotype. CIE and LI are clinically characterized by fine, whitish scales on a background of erythematous skin, and large, thick, dark scales over the entire body without serious background erythroderma, respectively. To date, a total of 56 ABCA12 mutations have been reported in 66 ARCI families including 48 HI, 10 LI, and 8 CIE families of African, European, Pakistani/Indian, and Japanese origin (online database: http://www.derm-hokudai.jp/ABCA12/). A total of 62.5% of reported ABCA12 mutations are expected to lead to truncated proteins. Most mutations in HI are truncation mutations and homozygous or compound heterozygous truncation mutations always results in HI phenotype. In CIE families, at least one mutation on each allele is typically a missense mutation. Combinations of missense mutations in the first ATP-binding cassette of ABCA12 underlie the LI phenotype. ABCA12 is a keratinocyte lipid transporter associated with lipid transport in lamellar granules, and loss of ABCA12 function leads to a defective lipid barrier in the stratum corneum, resulting in an ichthyotic phenotype. Recent work using mouse models confirmed ABCA12 roles in skin barrier formation.
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No. Sentence Comment
77 None of the LI mutations was demonstrated to cause HI phenotype, although one mutation p.Arg1514His was identified to result in both LI and CIE phenotypes (Supp. Table S1).
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ABCA12 p.Arg1514His 20672373:77:89
status: NEW83 Mutations in green letters lead to two distinct phenotypes, p.Arg1950Ter and p.Arg2482Ter both result in CIE and HI phenotypes; p.Arg1514His underlies both CIE and LI phenotypes.
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ABCA12 p.Arg1514His 20672373:83:130
status: NEW95 Only one mutation p.Arg1514His was reported to underlie both CIE and LI phenotypes (Supp. Table S1).
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ABCA12 p.Arg1514His 20672373:95:20
status: NEW[hide] ABCA12 is a major causative gene for non-bullous c... J Invest Dermatol. 2009 Sep;129(9):2306-9. Epub 2009 Mar 5. Sakai K, Akiyama M, Yanagi T, McMillan JR, Suzuki T, Tsukamoto K, Sugiyama H, Hatano Y, Hayashitani M, Takamori K, Nakashima K, Shimizu H
ABCA12 is a major causative gene for non-bullous congenital ichthyosiform erythroderma.
J Invest Dermatol. 2009 Sep;129(9):2306-9. Epub 2009 Mar 5., [PMID:19262603]
Abstract [show]
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No. Sentence Comment
45 (À) This study NBCIE8 52 M p.[Arg1514His]+[=] (À) This study NBCIE9 0 M (À) p.[Arg389His]+c.[2111delA] Akiyama et al. (2001a) NBCIE10 37 F p.[Thr345Pro]+[=] (À) Natsuga et al. (2007) NBCIE11 42 M p.[Ile1494Thr]+[?]
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ABCA12 p.Arg1514His 19262603:45:30
status: NEW