ABCMdb

ABCA12 p.Asn1380Ser

ClinVar:	c.4139A>G , p.Asn1380Ser D , Pathogenic
Predicted by SNAP2:	A: D (95%), C: D (95%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (95%), K: D (95%), L: D (95%), M: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: D (91%), T: D (95%), V: D (95%), W: D (95%), Y: D (95%),
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, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D,

[switch to compact view]
Comments [show]

None has been submitted yet.

Publications
[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.

Comments [show]

None has been submitted yet.

Sentences [show]
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). Login to comment
75 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. Login to comment
88 Four of the mutations (N1380S, G1381E, R1514H, E1539K) were situated in the first highly conserved ATP binding domain of the protein (Fig. 4). Login to comment

[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]

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
28 Patients 2 and 3 had compound heterozygosity of missense /splice-site mutations [(p.Arg986Trp)+(c.5940-1G>C), (p.Asn1380Ser)+(c.5128+ 3A>G), respectively]. Login to comment
29 Patient 4 had compound heterozygosity Table 1 Summary of mutation analysis of ABCA12 in the present study Patient Age, sex Mutation Maternal Paternal 1 3 years, girl Compound heterozygous p.Thr1575Pro (c.4723A>C) c.6031delG 2 9 years, girl Compound heterozygous p.Arg986Trp (c.2956C>T) c.5940-1G>C 3 4 months, boy Compound heterozygous p.Asn1380Ser (c.4139A>G) c.5128+3A>G 4 3 months, boy Compound heterozygous p.Thr1575Pro (c.4723A>C) p.Gly1651Ser (c.4951G>A) (a) (b) (c) (d) (e) Fig 1. Login to comment
38 Two recurrent mutations (p.Asn1380Ser and p.Gly1651Ser) have been reported previously in LI2.6 These mutations were not found in 200 normal, unrelated Japanese alleles. Login to 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] 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.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
50 The second most common reported ABCA12 mutation is a missense mutation p.Asn1380Ser in Walker A motif of the first ATP-binding cassette, which is essential for the transporter function of ABCA12 [Lefe`vre et al., 2003]. Login to comment
51 This missense mutation p.Asn1380Ser has been identified in five LI families from Africa (three families from Morocco and two families from Algeria) [Lefe`vre et al., 2003]. Login to comment
52 Haplotype analysis confirmed that p.Asn1380Ser is a founder mutation in the patients from Morocco/Algeria region [Lefe`vre et al., 2003]. Login to comment

[hide] Novel ABCA12 missense mutation p.Phe2144Ser underl... J Dermatol. 2013 Jul;40(7):581-2. doi: 10.1111/1346-8138.12169. Epub 2013 May 19. Shimizu Y, Sugiura K, Aoyama Y, Ogawa Y, Hitomi K, Iwatsuki K, Akiyama M
Novel ABCA12 missense mutation p.Phe2144Ser underlies congenital ichthyosiform erythroderma.
J Dermatol. 2013 Jul;40(7):581-2. doi: 10.1111/1346-8138.12169. Epub 2013 May 19., [PMID:23682801]

Abstract [show]

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
10 Oligonucleotide primers and polymerase chain reaction conditions used for amplification of all ABCA12 exons and exon-intron borders were originally derived from the report by Lef evre et al.3 Two heterozygous ABCA12 mutations were identified in the patient: the novel missense mutation c.6431T>C (p.Phe2144Ser) in exon 44, which was not detected in the 100 control alleles (50 individuals; data not shown), and the known missense mutation c.4139A>G (p.Asn1380Ser) in exon 28 (Fig. 1c). Login to comment
11 p.Asn1380Ser was previously reported as an LI-causative mutation.3 p.Asn1380Ser was present in the mother and p.Phe2144Ser was demonstrated as paternal (data not shown). Login to comment
14 The homozygous mutation p.Asn1380Ser and the compound heterozygous mutations p.Asn1380Ser and p.Gly1651Ser were previously reported to underlie typical LI phenotypes.3 In this regard, we hypothesized that the difference between p.Asn1380Ser/p.Gly1651Ser and p.Phe2144Ser may determine whether the phenotype is LI or CIE. Login to comment
27 The homozygous mutation p.Asn1380Ser and the compound heterozygous mutations p.Asn1380Ser and p.Gly1651Ser underlie lamellar ichthyosis (LI). Login to comment
28 Compound heterozygous mutations p.Asn1380Ser and p.Phe2144 underlie CIE (the present case; asterisk). Login to comment