ABCA12

ABCA12
Identifiers
Aliases	ABCA12, ARCI4A, ARCI4B, ICR2B, LI2, ATP binding cassette subfamily A member 12
External IDs	OMIM: 607800; MGI: 2676312; HomoloGene: 45441; GeneCards: ABCA12; OMA:ABCA12 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2q35 Start 214,931,542 bp End 215,138,626 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1|1 C3 Start 71,281,435 bp End 71,454,069 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in human penis skin of thigh skin of arm vulva skin of abdomen testicle skin of hip gonad cervix epithelium vagina Top expressed in esophagus lip embryo skin of external ear embryo zygote epidermis secondary oocyte spermatid hair follicle More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding transporter activity apolipoprotein A-I receptor binding ATPase activity protein binding signaling receptor binding ATP binding ATPase-coupled lipid transmembrane transporter activity lipid transporter activity ATPase-coupled transmembrane transporter activity Cellular component cytoplasm integral component of membrane cytosol membrane plasma membrane epidermal lamellar body intracellular membrane-bounded organelle Biological process surfactant homeostasis lipid transport ceramide transport establishment of skin barrier secretion by cell phospholipid efflux keratinization cellular homeostasis keratinocyte differentiation positive regulation of cholesterol efflux positive regulation of protein localization to cell surface lipid homeostasis regulated exocytosis lung alveolus development protein localization to plasma membrane transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 26154 74591 Ensembl ENSG00000144452 ENSMUSG00000050296 UniProt Q86UK0 E9Q876 RefSeq (mRNA) NM_015657 NM_173076 NM_175210 RefSeq (protein) NP_056472 NP_775099 NP_780419 Location (UCSC) Chr 2: 214.93 – 215.14 Mb Chr 1: 71.28 – 71.45 Mb PubMed search
Wikidata
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ATP-binding cassette sub-family A member 12 also known as ATP-binding cassette transporter 12 is a protein that in humans is encoded by the ABCA12 gene.

ABCA12 belongs to a group of genes called the ATP-binding cassette family, which makes proteins that transport molecules across cell membranes. The ABCA12 gene is active in some types of skin cells and in several other tissues, such as testis, placenta, lung, stomach, and fetal brain and liver. This protein appears to be essential for normal development of the skin, which provides a barrier between the body and its surrounding environment. It transports epidermoside, a glucosylceramide, out of the keratinocytes of the stratum corneum of the epidermis.

The ABCA12 gene is located on the long (q) arm of chromosome 2 between positions 34 and 35, from base pair 215,621,772 to base pair 215,828,656.

Clinical significance

Harlequin-type ichthyosis

Several mutations in the ABCA12 gene are known to cause harlequin-type ichthyosis. Most of these mutations are predicted to lead to an absence of ABCA12 protein or the production of an extremely small version of the protein that cannot transport lipids properly. A loss of functional ABCA12 protein causes numerous problems with the development of the epidermis before and after birth. Abnormalities in lipid transport prevent the skin from forming an effective barrier and result in the hard, thick scales characteristic of harlequin ichthyosis.

Lamellar ichthyosis type 2

Mutations in the ABCA12 gene also cause another severe skin disorder, lamellar ichthyosis type 2. People with this disorder have red, scaly, plate-like skin covering most of their bodies. The ABCA12 mutations that cause this disorder substitute one amino acid (a building block of proteins) for another amino acid in the ABCA12 protein. These mutations almost always occur in an important functional region of the protein (the region that binds to ATP, a molecule that supplies energy for chemical reactions). Changes in the structure of the ABCA12 protein likely disrupt its ability to transport lipids, which affects the development of skin before and after birth.

Further reading

• Lefévre 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 (September 2003). "Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2". Hum. Mol. Genet. 12 (18): 2369–78. doi:10.1093/hmg/ddg235. PMID 12915478.*Sakai K, Akiyama M, Sugiyama-Nakagiri Y, et al. (2007). "Localization of ABCA12 from Golgi apparatus to lamellar granules in human upper epidermal keratinocytes". Exp. Dermatol. 16 (11): 920–6. doi:10.1111/j.1600-0625.2007.00614.x. PMID 17927575. S2CID 23836833.
• Thomas AC, Tattersall D, Norgett EE, et al. (2009). "Premature terminal differentiation and a reduction in specific proteases associated with loss of ABCA12 in Harlequin ichthyosis". Am. J. Pathol. 174 (3): 970–8. doi:10.2353/ajpath.2009.080860. PMC 2665756. PMID 19179616.
• Yamanaka Y, Akiyama M, Sugiyama-Nakagiri Y, et al. (2007). "Expression of the keratinocyte lipid transporter ABCA12 in developing and reconstituted human epidermis". Am. J. Pathol. 171 (1): 43–52. doi:10.2353/ajpath.2007.061207. PMC 1941601. PMID 17591952.
• Thomas AC, Sinclair C, Mahmud N, et al. (2008). "Novel and recurring ABCA12 mutations associated with harlequin ichthyosis: implications for prenatal diagnosis". Br. J. Dermatol. 158 (3): 611–3. doi:10.1111/j.1365-2133.2007.08277.x. PMID 17986308. S2CID 10098614.
• Rose JE, Behm FM, Drgon T, et al. (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Mol. Med. 16 (7–8): 247–53. doi:10.2119/molmed.2009.00159. PMC 2896464. PMID 20379614.
• Dean M, Rzhetsky A, Allikmets R (2001). "The human ATP-binding cassette (ABC) transporter superfamily". Genome Res. 11 (7): 1156–66. doi:10.1101/gr.184901. PMID 11435397. S2CID 9528197.
• Jiang YJ, Lu B, Kim P, et al. (2008). "PPAR and LXR activators regulate ABCA12 expression in human keratinocytes". J. Invest. Dermatol. 128 (1): 104–9. doi:10.1038/sj.jid.5700944. PMID 17611579.
• Ohkubo T, Shibata N, Ohnuma T, et al. (2005). "No genetic association between ATP binding cassette proteins and Japanese sporadic Alzheimer's disease". Dement Geriatr Cogn Disord. 20 (2–3): 95–8. doi:10.1159/000086473. PMID 15980630. S2CID 25370003.
• Jiang YJ, Uchida Y, Lu B, et al. (2009). "Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor {delta} in human keratinocytes". J. Biol. Chem. 284 (28): 18942–52. doi:10.1074/jbc.M109.006973. PMC 2707228. PMID 19429679.
• Annilo T, Shulenin S, Chen ZQ, et al. (2002). "Identification and characterization of a novel ABCA subfamily member, ABCA12, located in the lamellar ichthyosis region on 2q34". Cytogenet. Genome Res. 98 (2–3): 169–76. doi:10.1159/000069811. PMID 12697999. S2CID 28012695.
• Akiyama M, Sugiyama-Nakagiri Y, Sakai K, et al. (2005). "Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer". J. Clin. Invest. 115 (7): 1777–84. doi:10.1172/JCI24834. PMC 1159149. PMID 16007253.
• Parmentier L, Clepet C, Boughdene-Stambouli O, et al. (1999). "Lamellar ichthyosis: further narrowing, physical and expression mapping of the chromosome 2 candidate locus". Eur. J. Hum. Genet. 7 (1): 77–87. doi:10.1038/sj.ejhg.5200271. PMID 10094194. S2CID 17929356.
• Kelsell DP, Norgett EE, Unsworth H, et al. (2005). "Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis". Am. J. Hum. Genet. 76 (5): 794–803. doi:10.1086/429844. PMC 1199369. PMID 15756637.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. S2CID 21903526.
• Mammalian Gene Collection Program Team; Strausberg, R. L.; Feingold, E. A.; Grouse, L. H.; et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Natsuga K, Akiyama M, Kato N, et al. (2007). "Novel ABCA12 mutations identified in two cases of non-bullous congenital ichthyosiform erythroderma associated with multiple skin malignant neoplasia". J. Invest. Dermatol. 127 (11): 2669–73. doi:10.1038/sj.jid.5700885. hdl:2115/32351. PMID 17508018.
• Sakai K, Akiyama M, Yanagi T, et al. (2009). "ABCA12 is a major causative gene for non-bullous congenital ichthyosiform erythroderma". J. Invest. Dermatol. 129 (9): 2306–9. doi:10.1038/jid.2009.23. PMID 19262603.
• Allikmets R, Gerrard B, Hutchinson A, Dean M (1996). "Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database". Hum. Mol. Genet. 5 (10): 1649–55. doi:10.1093/hmg/5.10.1649. PMID 8894702.
• Thomas AC, Cullup T, Norgett EE, et al. (2006). "ABCA12 is the major harlequin ichthyosis gene". J. Invest. Dermatol. 126 (11): 2408–13. doi:10.1038/sj.jid.5700455. PMID 16902423.

External links

• GeneCard
• ABCA12 protein, human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• ABCA12 human gene location in the UCSC Genome Browser.
• ABCA12 human gene details in the UCSC Genome Browser.