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.

MYOC Gene

Defintion:Myocilin, trabecular meshwork inducible glucocorticoid response

Official Symbol:MYOC

 Chromosome:1

 Location : 1q23-q24

Gene Size:17216 Bp  (169,871,179 to 169,888,395) Complement


No Exons:3

Description:

The MYOC gene provides instructions for producing a protein called myocilin. Myocilin is found in certain structures of the eye, called the trabecular meshwork and the ciliary body, that regulate the pressure within the eye (intraocular pressure). It is also found in various types of muscle. Myocilin's function is not well understood, but it may help to control the intraocular pressure through its action in the muscle tissue of the ciliary body.

Disease :
Early-onset glaucoma - caused by mutations in the MYOC gene
Approximately 10 percent to 33 percent of people with juvenile open-angle glaucoma have mutations in the MYOC gene. MYOC mutations have also been detected in some people with primary congenital glaucoma.

Mutations in the MYOC gene may alter the myocilin protein so that its interactions with other proteins are impeded. Defective myocilin that is not incorporated into functional complexes may accumulate in the trabecular meshwork and ciliary body. The excess protein may prevent sufficient flow of fluid from the eye, resulting in increased intraocular pressure and causing the signs and symptoms of early-onset glaucoma.

Individuals with mutations in both the MYOC and CYP1B1 genes may develop glaucoma at an earlier age than do those with mutations in only one of the genes.

GJB3 Gene

Definition:Gap junction protein, beta 3, 31kDa.

Official Symbol:GJB3

 Chromosome:1

 Location : 1p34

Gene Size:  5178 bp (35,019,377 to 35,024,554)


No Exons:

Description:

Gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell.Connexin 31 is found in several different tissues throughout the body, including the skin, the inner ear, and the nerve that connects the inner ear with the brain (the auditory nerve). Connexin 31 plays a role in the growth and maturation of the outermost layer of skin (the epidermis). The presence of this protein in the inner ear and auditory nerve suggests that it may be involved in hearing. Hearing requires the conversion of sound waves to electrical nerve impulses, which travel along the auditory nerve to the brain. The exact role of connexin 31 in the inner ear and auditory nerve is unclear.

Disease :

Mutations in this gene can cause non-syndromic deafness or erythrokeratodermia variabilis, a skin disorder. Alternative splicing results in multiple transcript variants encoding the same protein.

nonsyndromic deafness

    Researchers have identified a few GJB3 mutations in people with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNA2. DFNA2 deafness is inherited in an autosomal dominant manner, which means that one copy of the GJB3 gene in each cell is altered. A few GJB3 mutations have also been identified in people with autosomal recessive nonsyndromic deafness. This type of inheritance means that two copies of the GJB3 gene in each cell are altered. It is unclear, however, whether GJB3 mutations are the direct cause of hearing loss in individuals with either of these types of deafness.

    GJB3 mutations related to hearing loss alter the sequence of protein building blocks (amino acids) in connexin 31. Some mutations lead to missing amino acids in connexin 31, and other mutations replace one amino acid with an incorrect amino acid. These changes likely alter the 3-dimensional shape or size of connexin 31, which could disrupt the assembly or function of gap junctions. It is unclear how GJB3 mutations contribute to hearing loss.

GBA Gene

Defintion:Glucosidase, beta; acid (includes glucosylceramidase) also known as GCB; GBA1; GLUC


official Symbol:GBA


Chromosome:1

Location : 1q21


Gene Size: 10246 bp (153470867..153481112) complement



No Exons:12


Description:

This gene encodes a lysosomal membrane protein that cleaves the beta-glucosidic linkage of glycosylceramide, an intermediate in glycolipid metabolism.This enzyme is active in lysosomes, which are structures inside cells that act as recycling centers. Lysosomes use digestive enzymes to break down toxic substances, digest bacteria that invade the cell, and recycle worn-out cell components. Based on these functions, enzymes in the lysosome are sometimes called housekeeping enzymes. Beta-glucocerebrosidase is a housekeeping enzyme that helps break down a large molecule called glucocerebroside into a sugar (glucose) and a simpler fat molecule (ceramide).

Disease :

Mutations in this gene cause Gaucher disease, a lysosomal storage disease characterized by an accumulation of glucocerebrosides,It is found that more than 200 mutations occurs in GBA gene.Which causes Gaucher Disease,Most of the GBA mutations responsible for Gaucher disease change a single protein building block (amino acid) in beta-glucocerebrosidase, altering the structure of the enzyme and preventing it from working normally. Other mutations delete or insert genetic material in the GBA gene or lead to the production of an abnormally short, nonfunctional version of the enzyme.

Growing evidence suggests an association between GBA mutations and Parkinson disease or Parkinson-like disorders that affect movement and balance (parkinsonism). People with Gaucher disease have mutations in both copies of the GBA gene in each cell, while those with a mutation in just one copy of the gene are called carriers. Some studies suggest that people with Gaucher disease and GBA mutation carriers have an increased risk of developing Parkinson disease or parkinsonism.

Symptoms of Parkinson disease and parkinsonism result from the loss of nerve cells that produce dopamine. Dopamine is a chemical messenger that transmits signals within the brain to produce smooth physical movements. It remains unclear how GBA mutations lead to these disorders. Researchers speculate that GBA mutations may contribute to the faulty breakdown of toxic substances in nerve cells by impairing the function of lysosomes, or mutations may enhance the formation of abnormal protein deposits. As a result, toxic substances or protein deposits could accumulate and kill dopamine-producing nerve cells, leading to abnormal movements and balance problems.

GALE Gene

Defintion: The Official name of GALE  UDP-galactose-4-epimerase

Chromosome:1

Loaction :1p36-p35

Gene Size: 5206 bp( 23994676 to 23999881)


No Exons: 12

Description:
The GALE gene provides instructions for making an enzyme called UDP-galactose-4-epimerase. This enzyme enables the body to process a simple sugar called galactose, which is present in small amounts in many foods. Galactose is primarily part of a larger sugar called lactose,


Disease :
Mutations in this gene result in epimerase-deficiency galactosemia, also referred to as galactosemia type 3, More than 20 mutations in the GALE gene have been identified in people with a form of galactosemia known as type III or galactose epimerase deficiency,a disease characterized by liver damage, early-onset cataracts, deafness and mental retardation, with symptoms ranging from mild ('peripheral' form) to severe ('generalized' form). Multiple alternatively spliced transcripts encoding the same protein have been identified.

FMO3 Gene

Defintion:The official name of this gene is “flavin containing monooxygenase 3.”

Chromosome:1

Position:1q23-q25

Gene Size:  26924 bp(169,326,659 to 169,353,582)

No of Exons: 9

Description:

The FMO3 gene provides instructions for making an enzyme that is part of a larger enzyme family called flavin-containing monooxygenases (FMOs). These enzymes break down compounds that contain nitrogen, sulfur, or phosphorus. The FMO3 enzyme, which is made chiefly in the liver, is responsible for breaking down nitrogen-containing compounds derived from the diet. One of these compounds is trimethylamine, which is the molecule that gives fish their fishy smell. Trimethylamine is produced as bacteria in the intestine help digest certain proteins obtained from eggs, liver, legumes (such as soybeans and peas), certain kinds of fish, and other foods. The FMO3 enzyme normally converts fishy-smelling trimethylamine into another compound, trimethylamine-N-oxide, which has no odor. Trimethylamine-N-oxide is then excreted from the body in urine.

Researchers believe that the FMO3 enzyme also plays a role in processing some types of drugs. For example, this enzyme is likely needed to break down the anticancer drug tamoxifen, the pain medication codeine, the antifungal drug ketoconazole, and certain medications used to treat depression (antidepressants). The FMO3 enzyme may also be involved in processing nicotine, an addictive chemical found in tobacco. Normal variations (polymorphisms) in the FMO3 gene may affect the enzyme's ability to break down these substances. Researchers are working to determine whether FMO3 polymorphisms can help explain why people respond differently to certain drugs.

Disease :
Trimethylaminuria

More than 25 mutations in the FMO3 gene have been identified in people with trimethylaminuria. Most of these mutations lead to the production of a small, nonfunctional version of the FMO3 enzyme. Other mutations change single building blocks (amino acids) used to build the enzyme, which alters its shape and disrupts its function. Without enough functional FMO3 enzyme, the body is unable to convert trimethylamine into trimethylamine-N-oxide effectively. As a result, trimethylamine builds up in the body and is released in an affected person's sweat, urine, and breath. The excretion of this compound is responsible for the strong body odor characteristic of trimethylaminuria. Studies suggest that diet and stress also play a role in determining the intensity of the fish-like odor.

F5 gene

Defintion:
Factor V is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor.

Chromosome:1

Position:1q23

Gene Size: 74578 bp (167747816 to 167822393)Complement


No of Exons: 25

Description:

This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance.

Disease :
factor V Leiden thrombophilia

A specific mutation in the F5 gene is responsible for factor V Leiden thrombophilia. Thrombophilia is an increased tendency to form abnormal blood clots in blood vessels. The factor V Leiden mutation changes a single protein building block (amino acid) in the factor V protein. Specifically, this mutation replaces the amino acid arginine with the amino acid glutamine at protein position 506 (written as Arg506Gln). The factor V Leiden mutation affects one of the sites where APC cleaves the factor Va protein, slowing the rate at which factor V is inactivated. This genetic change also prevents factor V from working with APC to inactivate factor VIIIa. As a result, the clotting process continues longer than usual, increasing the chance of developing abnormal blood clots.

    Some mutations in the F5 gene prevent the production of a functional factor V protein or decrease the amount of the protein in the bloodstream. When present in two copies of the F5 gene, these mutations lead to a rare condition called factor V deficiency or parahemophilia. A reduced amount of functional factor V prevents blood from clotting normally, causing episodes of abnormal bleeding that can range from mild to severe.

    A few people have been reported with the factor V Leiden mutation (Arg506Gln) in one copy of the F5 gene in each cell and a mutation associated with factor V deficiency in the other copy of F5. The factor V Leiden mutation results in the production of an abnormal factor V protein that is resistant to inactivation by APC, while the other mutation prevents the production of any factor V protein. People with this combination of mutations appear to have a risk of developing abnormal blood clots similar to the risk faced by people who have two copies of the factor V Leiden mutation. This condition is known as pseudo-homozygous APC resistance.