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Normal Function
The ABCA12 gene provides instructions for making a protein known as an ATP-binding cassette (ABC) transporter. ABC transporter proteins carry many types of molecules across cell membranes. In particular, the ABCA12 protein plays a major role in transporting fats (lipids) and enzymes in cells that make up the outermost layer of skin (the epidermis). This transport of molecules is needed to maintain the layers of lipids within the epidermis that are necessary to prevent water loss (dehydration) and for normal development of the skin.
Health Conditions Related to Genetic Changes
Harlequin ichthyosis
Many variants (also known as mutations) in the ABCA12 gene have been identified in people with harlequin ichthyosis. This skin condition is characterized by hard, thick scales that are present at birth; excessive dehydration; and increased risk of infections.
Most ABCA12 gene variants result in the production of an abnormally short protein that cannot transport lipids properly. Individuals with ABCA12 gene variants that result in a complete absense of ABCA12 protein often have the most severe skin problems and tend not to survive past infancy. In people with abnormal or nonfunctional ABCA12 protein, a lack of lipid transport causes numerous problems with the development of the epidermis before and after birth. Specifically, it prevents the skin from forming an effective barrier, and leads to the skin problems characteristic of harlequin ichthyosis.
Nonbullous congenital ichthyosiform erythroderma
Variants in the ABCA12 gene have been found to cause nonbullous congenital ichthyosiform erythroderma (NBCIE). This condition affects the skin and causes redness; the development of fine, white scales; an increased risk of infections; and dehydration. These skin abnormalities tend to be less severe than those in harlequin ichthyosis (described above).
Most of the variants that cause NBCIE change single protein building blocks (amino acids) in the ABCA12 protein. These variants likely lead to the production of a protein with reduced function, which impairs lipid transport and the formation of the lipid layers within the epidermis. Problems with this protective barrier underlie the skin abnormalities and other features of NBCIE.
More About This Health ConditionLamellar ichthyosis
MedlinePlus Genetics provides information about Lamellar ichthyosis
More About This Health ConditionOther Names for This Gene
- ABCAC_HUMAN
- ATP-binding cassette 12
- ATP-binding cassette transporter 12
- ATP-binding cassette, sub-family A (ABC1), member 12
- ATP-binding cassette, sub-family A, member 12
- ICR2B
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- 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. Citation on PubMed
- Kelsell DP, Norgett EE, Unsworth H, Teh MT, Cullup T, Mein CA, Dopping-Hepenstal PJ, Dale BA, Tadini G, Fleckman P, Stephens KG, Sybert VP, Mallory SB, North BV, Witt DR, Sprecher E, Taylor AE, Ilchyshyn A, Kennedy CT, Goodyear H, Moss C, Paige D, Harper JI, Young BD, Leigh IM, Eady RA, O'Toole EA. Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Am J Hum Genet. 2005 May;76(5):794-803. doi: 10.1086/429844. Epub 2005 Mar 8. Citation on PubMed or Free article on PubMed Central
- 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. doi: 10.1093/hmg/ddg235. Epub 2003 Jul 15. Citation on PubMed
- Nawaz S, Tariq M, Ahmad I, Malik NA, Baig SM, Dahl N, Klar J. Non-bullous congentital ichthyosiform erythroderma associated with homozygosity for a novel missense mutation in an ATP binding domain of ABCA12. Eur J Dermatol. 2012 Mar-Apr;22(2):178-81. doi: 10.1684/ejd.2011.1638. Citation on PubMed
- Richard G. Autosomal Recessive Congenital Ichthyosis. 2001 Jan 10 [updated 2023 Apr 20]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1420/ Citation on PubMed
- 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. doi: 10.1038/jid.2009.23. Epub 2009 Mar 5. No abstract available. Citation on PubMed
- Scott CA, Rajpopat S, Di WL. Harlequin ichthyosis: ABCA12 mutations underlie defective lipid transport, reduced protease regulation and skin-barrier dysfunction. Cell Tissue Res. 2013 Feb;351(2):281-8. doi: 10.1007/s00441-012-1474-9. Epub 2012 Aug 4. Citation on PubMed
- Thomas AC, Cullup T, Norgett EE, Hill T, Barton S, Dale BA, Sprecher E, Sheridan E, Taylor AE, Wilroy RS, DeLozier C, Burrows N, Goodyear H, Fleckman P, Stephens KG, Mehta L, Watson RM, Graham R, Wolf R, Slavotinek A, Martin M, Bourn D, Mein CA, O'Toole EA, Kelsell DP. ABCA12 is the major harlequin ichthyosis gene. J Invest Dermatol. 2006 Nov;126(11):2408-13. doi: 10.1038/sj.jid.5700455. Epub 2006 Aug 10. Citation on PubMed
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