Friday, June 22, 2012

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 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.


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 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.

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