Defective ABCA12 does not transport lipids from cytosol to extracellular region

Stable Identifier
Reaction [transition]
Homo sapiens
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ATP-binding cassette sub-family A member 12 (ABCA12) is thought to function as an epidermal keratinocyte lipid transporter. Lipids such as glucosylceramides and gangliosides form extracellular lipid layers in the stratum corneum of the epidermis, essential for skin barrier function. Defects in ABCA12 results in the loss of the skin lipid barrier, leading to autosomal recessive congenital ichthyosis 4B (ARCI4B; MIM:242500, aka harlequin ichthyosis, HI). ARCI4B shows the most severe phenotype of the congenital ichthyoses, with newborns having a thick covering of armour-like scales. Mutations causing ARCI4B include V2442Sfs*22, K1671Ifs*4, D2363N, G1179R and R287* (Kelsell et al. 2005, Thomas et al. 2006, Castiglia et al. 2009).
Literature References
PubMed ID Title Journal Year
16902423 ABCA12 is the major harlequin ichthyosis gene

Stephens, KG, Taylor, AE, Martin, M, O'Toole, EA, Hill, T, Wolf, R, Bourn, D, Mehta, L, Cullup, T, Wilroy, RS, DeLozier, C, Graham, R, Mein, CA, Kelsell, DP, Norgett, EE, Fleckman, P, Goodyear, H, Sheridan, E, Barton, S, Thomas, AC, Watson, RM, Sprecher, E, Burrows, N, Slavotinek, A, Dale, BA

J. Invest. Dermatol. 2006
15756637 Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis

Cullup, T, Tadini, G, Stephens, KG, Witt, DR, O'Toole, EA, Unsworth, H, Ilchyshyn, A, Mallory, SB, Taylor, AE, Kennedy, CT, Teh, MT, Harper, JI, Sybert, VP, Mein, CA, Kelsell, DP, Norgett, EE, North, BV, Fleckman, P, Goodyear, H, Leigh, IM, Eady, RA, Sprecher, E, Dopping-Hepenstal, PJ, Moss, C, Young, BD, Dale, BA, Paige, D

Am. J. Hum. Genet. 2005
19664001 Trisomic rescue causing reduction to homozygosity for a novel ABCA12 mutation in harlequin ichthyosis

Castiglia, D, Zambruno, G, Pisaneschi, E, Sommi, M, Magnani, C, Covaciu, C, Fischer, J, Castori, M

Clin. Genet. 2009
Catalyst Activity

lipid transporter activity of ABCA12 mutants [plasma membrane]

Normal reaction
Functional status

Loss of function of ABCA12 mutants [plasma membrane]

Name Identifier Synonyms
autosomal recessive congenital ichthyosis DOID:0060655 lamellar ichthyosis, Ichthyosiform erythroderma, Alligator skin, nonbullous congenital ichthyosiform erythroderma, Congenital non bullous ichthyosiform erythroderma
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