ABCA12 Gene

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.

Gene Family……

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]

Location……

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 2^nd 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.

Function…….

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 1^st group includes 7 genes dispersed on 6 different chromosomes (ABCA1, ABCA2, ABCA3, ABCA4, ABCA7, ABCA12 and ABCA13) where as the 2^nd 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.