As we discuss earlier that harlequin Ichthyosis (HI) is caused by the mutation in ABCA1 gene. Let’s try to understand the genetics behind this mutation and its co-relation with the rare genetic disorder HI.
What is the official name of ABCA12 gene?
The official name of ABCA12 gene is ATP-binding cassette, subfamily A (ABC1), member 12. 'ABCA12' 'is the gene’s official symbol.
ABCA12 is a member of the “ATP-binding cassette (ABC) transporters”. It also belongs to a family of genes called “ATPase Superfamily (ATP)”.
[A gene family is a group of genes that share important characteristics. In many cases, gene in a family share a similar sequence of DNA building blocks neucleotide. These genes provides instruction for making products like proteins that have a similar structure of function]
The ABCA 12 gene is located on the Long (q) arm of Chromosome 2 at position 34.
Cytogenetic Location: 2q34
Molecular Location in Chromosome 2: base pairs (bp) 215,796,265 to 216,003,150.
Chromosome 2: Human has 23 pairs of chromosome i. e. 23 x 2 = 46 number of chromosome (each copy inherited from each biological parent). Chromosome 2 is the 2nd largest human chromosome, spanning more than 243 million building blocks of DNA base-pare and representing almost 8% of Total DNA in cells. Chromosome 2 is likely to contain 1300 to 1400 genes among the estimated 20,000-25,000 total genes in human genome.
The ATP-binding cassette (ABC) gene represents the largest family of ‘Transmembrane’ (TI) proteins. The ABC super-family are grouped into 7 major sub-families depending on the alignment of the amino acid (ã ã) sequence in the nucleotide-binding folds (NBF) and phylogenetic analysis……
1. ABCA (ABC1)
2. ABCB (MDR/ TAP)
3. ABCC (CFTR/ MRP)
4. ABCD (ALD)
5. ABCE (OABP)
6. ABCF (GCN20)
7. ABCG (White)
The human ABCA subfamily comprises 12 full transporters that are further divided into 2 subgroups based on the phylogenetic analysis and intron structure. The 1st group includes 7 genes dispersed on 6 different chromosomes (ABCA1, ABCA2, ABCA3, ABCA4, ABCA7, ABCA12 and ABCA13) where as the 2nd group contains 5 genes (ABCA5, ABCA6, ABCA8, ABCA9 and ABCA10) arranged in a cluster on chromosome 17q24.
ABC transporters bind and hydrolyze ATP to transport various molecules across a limiting membrane or into a vesicle. The ABCA subfamily membranes play a major role in transporting lipids (fats) in cells which make up the outer most layer of skin (the Epidermis). ABCA12 was recognized as a key molecule in keratinocyte lipid transport. ABCA12 is a keratinocyte transmembrane lipid transporter protein associated with lipid transport in lamellar granules to the apical surface of granular layer keratinocytes.