ABCMdb

ABCA12 p.Ile1494Thr

Predicted by SNAP2:	A: D (85%), C: D (80%), D: D (91%), E: D (95%), F: D (91%), G: D (95%), H: D (91%), K: D (95%), L: N (78%), M: N (61%), N: D (91%), P: D (95%), Q: D (91%), R: D (95%), S: D (91%), T: D (91%), V: D (59%), W: D (91%), Y: D (80%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D,

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Publications
[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]

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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. Login to comment

[hide] The roles of ABCA12 in keratinocyte differentiatio... Dermatoendocrinol. 2011 Apr;3(2):107-12. Epub 2011 Apr 1. Akiyama M
The roles of ABCA12 in keratinocyte differentiation and lipid barrier formation in the epidermis.
Dermatoendocrinol. 2011 Apr;3(2):107-12. Epub 2011 Apr 1., [PMID:21695020]

Abstract [show]
ABCA12 is a member of the large superfamily of ATP-binding cassette (ABC) transporters, which bind and hydrolyze ATP to transport various molecules across limiting membranes or into vesicles. The ABCA subfamily members are thought to be lipid transporters. ABCA12 is a keratinocyte transmembrane lipid transporter protein associated with the transport of lipids in lamellar granules to the apical surface of granular layer keratinocytes. Extracellular lipids, including ceramide, are thought to be essential for skin barrier function. ABCA12 mutations are known to underlie the three main types of autosomal recessive congenital ichthyoses: harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma. ABCA12 mutations lead to defective lipid transport via lamellar granules in the keratinocytes, resulting in malformation of the epidermal lipid barrier and ichthyosis phenotypes. Studies of ABCA12-deficient model mice indicate that lipid transport by ABCA12 is also indispensable for intact differentiation of keratinocytes.

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36 One patient was homozygous for the splice site mutation c.3295-2A>G4 and another was compound heterozygous for p.Ser387Asn and p.Thr1387del.29 Only one heterozygous mutation, p.Ile1494Thr, was identified in the other patient.30 Cultured keratinocytes from all three patients showed apparently disturbed glucosylceramide transport, although this assay is not quantitative. Login to comment
37 One patient was homozygous for the splice site mutation c.3295-2A>G4 and another was compound heterozygous for p.Ser387Asn and p.Thr1387del.29 Only one heterozygous mutation, p.Ile1494Thr, was identified in the other patient.30 Cultured keratinocytes from all three patients showed apparently disturbed glucosylceramide transport, although this assay is not quantitative. Login to comment

[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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107 Only one heterozygous mutation p.Ile1494Thr was identified in the other patient [Natsuga et al., 2007]. Login to comment

[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]

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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]+[?] Login to comment

[hide] The roles of ABCA12 in epidermal lipid barrier for... Biochim Biophys Acta. 2014 Mar;1841(3):435-40. doi: 10.1016/j.bbalip.2013.08.009. Epub 2013 Aug 15. Akiyama M
The roles of ABCA12 in epidermal lipid barrier formation and keratinocyte differentiation.
Biochim Biophys Acta. 2014 Mar;1841(3):435-40. doi: 10.1016/j.bbalip.2013.08.009. Epub 2013 Aug 15., [PMID:23954554]

Abstract [show]
ATP-binding cassette (ABC) transporters form a large superfamily of transporters that bind and hydrolyze ATP to transport various molecules across limiting membranes or into vesicles. The ABCA subfamily members are thought to transport lipid materials. ABCA12 is a keratinocyte transmembrane lipid transporter protein associated with the transport of lipids via lamellar granules. ABCA12 is considered to transport lipids including ceramides to form extracellular lipid layers in the stratum corneum of the epidermis, which is essential for skin barrier function. ABCA12 mutations are known to underlie the three major types of autosomal recessive congenital ichthyoses: harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma. ABCA12 mutations result in defective lipid transport via lamellar granules in the keratinocytes, leading to ichthyosis phenotypes from malformation of the stratum corneum lipid barrier. Studies on ABCA12-deficient bioengineered models have revealed that lipid transport by ABCA12 is required for keratinocyte differentiation and epidermal morphogenesis. Defective lipid transport due to loss of ABCA12 function leads to the accumulation of intracellular lipids, including glucosylceramides and gangliosides, in the epidermal keratinocytes. The accumulation of gangliosides seems to result in the apoptosis of Abca12(-/-) keratinocytes. It was reported that AKT activation occurs in Abca12(-/-) granular-layer keratinocytes, which suggests that AKT activation serves to prevent the cell death of Abca12(-/-) keratinocytes. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

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No. Sentence Comment
84 Only one heterozygous mutation, p.Ile1494Thr, was identified in the other patient [39]. Login to comment