DIRAS3 Gene

Defintion:
DIRAS family, GTP-binding RAS-like 3,

Chromosome:1

Position:1p31

Gene Size: 4816 bp  (68289048 to68284233 Complement)

No of Exons: Not Known

Description:

DIRAS3 gene is a member of the Ras Superfamily ,Genes in this family provide instructions for making proteins that control cell growth and maturation. The DIRAS3 protein differs from other proteins in the Ras family in that it suppresses the growth of cells, whereas other Ras family proteins encourage cell growth. Genes that suppress cell growth and division are known as tumor suppressor genes. The proteins made from these genes keep cells from growing and dividing too fast or in an uncontrolled way.

Disease :

Research has shown that the tumor suppressor gene DIRAS3 is often downregulated in breast cancer cells, which means its activity is drastically reduced. In some cases, the gene is totally inactivated or lost. Because of genomic imprinting, cells normally have only one working copy of the DIRAS3 gene, the paternal copy. If this copy of the gene is inactivated or lost, cells produce little or no functional DIRAS3 protein. Without enough of this protein, cells can grow and divide too fast and in an uncontrolled manner. This abnormal cell division likely contributes to the growth and progression of cancerous tumors.Loss or inactivation of the paternal copy of the DIRAS3 gene is also associated with ovarian cancer. As in breast cancer cells, a shortage of the DIRAS3 protein may allow certain cells in the ovaries to grow and divide too fast and in an uncontrolled manner. This abnormal cell division is associated with the growth and progression of cancerous tumors. Downregulation of the DIRAS3 gene has also been reported in certain forms of uterine cancer, pancreatic cancer, lung cancer, and a cancer of the thyroid gland called follicular thyroid carcinoma.

DBT Gene

Definition:Dihydrolipoamide branched chain transacylase E2, also known as DBT, is a human gene

Chromosome: 1
Position:1p31
Size Of Gene: 62932 bp (100425066 to100487997)
No Exons : 11
Description

The branched-chain alpha-keto acid dehydrogenase complex (BCKD) is an inner-mitochondrial enzyme complex involved in the breakdown of the branched-chain amino acids isoleucine, leucine, and valine. The BCKD complex is thought to be composed of a core of 24 transacylase (E2) subunits, and associated decarboxylase (E1), dehydrogenase (E3), and regulatory subunits. This gene encodes the transacylase (E2) subunit. Mutations in this gene result in maple syrup urine disease, type 2. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

Function:

The DBT gene provides instructions for making part of an enzyme complex (a group of enzymes that work together) called branched-chain alpha-keto acid dehydrogenase, or BCKD. Specifically, the protein made by the DBT gene forms an essential part of the enzyme complex called the E2 component.The BCKD enzyme complex is responsible for one step in the normal breakdown of three protein building blocks (amino acids). These amino acids—leucine, isoleucine, and valine—are obtained from the diet. They are present in many kinds of food, particularly protein-rich foods such as milk, meat, and eggs. The BCKD enzyme complex is active in mitochondria, which are specialized structures inside cells that serve as energy-producing centers. The breakdown of leucine, isoleucine, and valine produces molecules that can be used for energy.

Disease:

More than 25 mutations in the DBT gene have been identified in people with maple syrup urine disease, most often in individuals with milder variants of the disorder. Mutations in the DBT gene include changes in single DNA building blocks (base pairs) and insertions or deletions of a small amount of DNA in the DBT gene. These mutations disrupt the normal function of the E2 component, preventing the BCKD enzyme complex from breaking down leucine, isoleucine, and valine. As a result, these amino acids and their byproducts build up in the body. Because this accumulation is toxic to tissues and organs, it leads to the signs and symptoms of maple syrup urine disease.

Short Introduction to Maple Syrup Urine Disease (MSUD)