HMGCL Gene

Defintion:3-hydroxymethyl-3-methylglutaryl-Coenzyme

Official Symbol:HMGCL

 Chromosome:1

 Location : 1p36.1-p35

Gene Size: 23583 bp complement(24000954..24024536)


No Exons: 9

Description:

The HMGCL gene provides instructions for making an enzyme that is found in mitochondria (the energy-producing centers inside cells). This enzyme, called 3-hydroxymethyl-3-methylglutaryl-coenzyme A (CoA) lyase, plays an essential role in breaking down proteins and fats from the diet. Specifically, 3-hydroxymethyl-3-methylglutaryl-CoA lyase is needed to process leucine, an amino acid used as a building block in many enzymes and other proteins. This enzyme is also involved in making ketones when fat is broken down by the body. These reactions produce molecules that are later used for energy.

Disease :

Many of the identified HMGCL mutations change the amino acids used as building blocks in the enzyme 3-hydroxymethyl-3-methylglutaryl-CoA lyase. Other mutations cause the production of an abnormally shortened enzyme that is missing critical components. All of these mutations disrupt the normal function of 3-hydroxymethyl-3-methylglutaryl-CoA lyase. As a result, leucine cannot be processed and ketones cannot be made properly. Because of incomplete processing, certain chemical byproducts (organic acids) can build up and cause the blood to become too acidic (metabolic acidosis). In addition, a lack of ketones causes blood sugar to become dangerously low (hypoglycemia). The effects of metabolic acidosis and hypoglycemia can damage the brain and nervous system.

HFE2 Gene

Defintion:Hemochromatosis type 2 (juvenile).

Official Symbol:HFE2

 Chromosome:1

 Location : 1q21.1

Gene Size: 4268 bp (144124635 to 144128902)


No Exons: 4

Description:

HFE2 gene provides instructions for making a protein called hemojuvelin. This protein is made in the liver, heart, and muscles used for movement (skeletal muscles). Researchers recently discovered that hemojuvelin plays a role in maintaining iron balance in the body. Although its exact function is unclear, hemojuvelin appears to regulate the levels of another protein called hepcidin. Hepcidin also plays a key role in maintaining proper iron levels in the body

Disease : 
Hemochromatosis - caused by mutations in the HFE2 gene

    Researchers have identified more than 20 HFE2 mutations that cause type 2 hemochromatosis, a form of the disorder that begins during childhood or adolescence. Most HFE2 mutations change one of the protein building blocks (amino acids) used to make hemojuvelin. Most frequently, the amino acid glycine is replaced by the amino acid valine at protein position 320 (written as Gly320Val). Other mutations create a premature stop signal in the instructions for making the hemojuvelin protein. As a result, an abnormally small protein is made.

A video about hemochromatosis

    Mutations in the HFE2 gene lead to an altered hemojuvelin protein that cannot function properly. Without adequate hemojuvelin, levels of the protein hepcidin are reduced and iron balance is disturbed. As a result, too much iron is absorbed during digestion, which leads to iron overload and damage to tissues and organs in the body.