ATP-binding cassette sub-family A member 12 also known as ATP-binding cassette transporter 12 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''ABCA12''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
''ABCA12'' belongs to a group of genes called the
ATP-binding cassette family, which makes proteins that transport molecules across
cell membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
s. The ''ABCA12'' gene is active in some types of
skin cells and in several other tissues, such as
testis
A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is Homology (biology), homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of Androgen, androgens, p ...
,
placenta
The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...
,
lung
The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
,
stomach
The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...
, and fetal brain and liver. This protein appears to be essential for normal development of the
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different ...
, which provides a barrier between the body and its surrounding environment. It transports
epidermoside, a
glucosylceramide
Glucocerebroside (also called glucosylceramide) is any of the cerebrosides in which the monosaccharide head group is glucose.
Research conducted on glucocerebrosides has shown that glucocerebrosides help support cellular functions in humans, ...
, out of the keratinocytes of the
stratum corneum
The stratum corneum (Latin language, Latin for 'horny layer') is the outermost layer of the epidermis (skin), epidermis. Consisting of dead tissue, it protects underlying tissue from infection, dehydration, chemicals and mechanical stress. It is ...
of the
epidermis
The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...
.
The ''ABCA12'' gene is located on the long (q) arm of
chromosome 2
Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost ei ...
between positions 34 and 35, from
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
215,621,772 to base pair 215,828,656.
Clinical significance
Harlequin-type ichthyosis
Several
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
s in the ''ABCA12'' gene are known to cause
harlequin-type ichthyosis
Harlequin-type ichthyosis is a genetic disorder that results in thickened skin over nearly the entire body at birth. The skin forms large, diamond/trapezoid/rectangle-shaped plates that are separated by deep cracks. These affect the shape of th ...
.
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
Lamellar ichthyosis, also known as ichthyosis lamellaris and nonbullous congenital ichthyosis, is a rare inherited skin disorder, affecting around 1 in 600,000 people.
Presentation
Affected babies are born in a collodion membrane – a shiny, wa ...
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
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
(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.
References
Further reading
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External links
GeneCard*
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{{DEFAULTSORT:Abca12
ATP-binding cassette transporters