ABCA12Gen

ABCA12Gen, also known as ABCA12, is a protein-coding gene in humans that encodes the ATP-binding cassette transporter ABCA12, a member of the ABC transporter superfamily. The gene is located on chromosome 15q24.1 and produces a large transmembrane protein with two nucleotide-binding domains and two transmembrane domains, a typical architecture of the ABCA subfamily. ABCA12 expression is highest in epidermal keratinocytes, with detectable levels in other tissues at lower abundance.

Functionally, ABCA12 plays a critical role in lipid transport within skin cells. The protein localizes to lamellar bodies, specialized secretory organelles in keratinocytes that deliver lipids to the outermost skin layer. By transporting ceramides and related lipids, ABCA12 contributes to the formation and maintenance of the stratum corneum lipid barrier, which is essential for preventing dehydration and protecting against environmental insults. Proper lipid sorting and lamellar body biogenesis depend on ABCA12 activity.

Clinical significance is most clearly demonstrated by autosomal recessive disorders caused by pathogenic variants in ABCA12. Biallelic mutations lead to ichthyoses, most notably harlequin ichthyosis, a severe congenital skin condition characterized by thickened, plate-like scales and significant barrier dysfunction. Less severe but related phenotypes include nonbullous congenital ichthyosiform erythroderma. Carriers are typically asymptomatic. The range of mutations includes frameshift, nonsense, and missense changes that disrupt protein function or stability.

In research and diagnostics, ABCA12 is studied for its role in skin barrier formation and lipid organization. Genetic testing for ABCA12 variants is used to diagnose ABCA12-related ichthyoses, inform prognosis, and guide management. Animal models, including knockout mice, support its essential role in epidermal barrier integrity and lipid transport.