PPOX Gene

 PPOX Gene provides informations to produce an enzyme called protoporphyrinogen oxidase ,This enzyme is responsible for the seventh step in the production of heme, the iron-containing part of hemoglobin.Hemoglobin is the oxygen-carrying protein in red blood cells. Each step in heme production is controlled by a different enzyme, each of which is produced from a single gene. Protoporphyrinogen oxidase removes hydrogen atoms from protoporphyrinogen IX (the product of the sixth step in the production of heme) to form protoporphyrin IX. One additional enzyme modifies protoporphyrin IX before it becomes heme. The heme molecule is incorporated into hemoglobin and packaged into red blood cells, or it is used in the liver for the production of certain liver enzymes.

Location

PPOX gene is present in human chromosome1 and its coded from the region 159402818 to 159407634,the cytogenetic location 1q22, the gene size is 4817 bp with 13 exonic regions

Disorder:

Mutations in this gene causes a  porphyria disorder

More than 100 mutations that cause a form of porphyria called variegate porphyria have been identified in the PPOX gene. A particular mutation that changes one of the building blocks (amino acids) used to make protoporphyrinogen oxidase is found in about 95 percent of South African families with variegate porphyria. Specifically, this genetic change substitutes the amino acid tryptophan for the amino acid arginine at position 59 (written as Arg59Trp or R59W). Mutations in the PPOX gene reduce the activity of protoporphyrinogen oxidase, allowing byproducts of heme production to build up in the body. This buildup, in combination with nongenetic factors (such as certain drugs, alcohol, and dieting), causes this type of porphyria.

PLOD1 Gene

The official name PLOD1 gene procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1,the Gene provides informations to produce an enzyme called lysyl hydroxylase 1,Lysyl hydroxylase is a membrane -homodimeric protein localized to the citernae of the endoplasmic reticulum.This enzyme modifies a particular amino acid called lysine, which is one of the building blocks used to make proteins. Specifically, lysyl hydroxylase 1 adds a single oxygen atom to a hydrogen atom to create a charged molecule called a hydroxyl group,The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks,Cross-links between these molecules allow collagen to form networks of strong, slender fibrils, which are an important part of the normal structure of connective tissue.

Location

PLOD1 gene is present in human chromosome1 and it is coded from the region from 1917333 to 11958181,the cytogenetic location 1p36.3-p36.2,tHe gene size is 40849 bp with 19 exons

Disease

Mutaions in this gene causes a Ehlers-Danlos syndrome.Researchers have identified more than 20 mutations in PLOD1 gene in affected persons,These mutations cause a form of Ehlers-Danlos syndrome called the kyphoscoliosis type,The most common mutation duplicates a large portion of the gene, resulting in the production of a nonfunctional version of the lysyl hydroxylase 1 enzyme. Several other mutations introduce premature stop signals that prevent the gene from making any functional enzyme. A loss of lysyl hydroxylase 1 activity impairs cross-linking between collagen molecules. This disruption in the network of collagen fibrils weakens connective tissues, causing the signs and symptoms of Ehlers-Danlos syndrome.

PINK1 gene

The official name of this gene is PTEN induced putative kinase 1,Gene provides informations to produce serine/threonine protein kinase that localizes to mitochondria,it is function of PTEN induced putative kinase 1 is not fully understood. It appears to help protect mitochondria from malfunctioning during periods of cellular stress, such as unusually high energy demands,Researchers believe that two specialized regions of PTEN induced putative kinase 1 are essential for the protein to function properly. One region, called the mitochondrial-targeting motif, serves as a delivery address. The protein is produced outside the mitochondria, and this motif helps ensure that it is delivered to the mitochondria. Another region, called the kinase domain, probably carries out the protein's protective function.

Location :PINK1 gene is present chromosome 1 and coded from 20,832,534 to 20,850,590 region ,the cytogenetic location is 1p36 ,The gene size is 18057 bp with 8 exons.

Disease:

Researchers have identified more than 20 PINK1 mutations that cause early-onset Parkinson disease. Some mutations change one of the protein building blocks (amino acids) used to make PTEN induced putative kinase 1. Other mutations lead to an abnormally small version of the protein. Many PINK1 mutations alter or eliminate the kinase domain, leading to a loss of protein function. At least one mutation affects the mitochondrial-targeting motif and may disrupt delivery of the protein to mitochondria. With reduced or absent PTEN induced putative kinase 1 activity, mitochondria may malfunction, particularly when cells are stressed. Cells can die if power is not provided for essential activities. It is unclear how PINK1 mutations cause the selective death of nerve cells that characterizes Parkinson disease.

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PARK7 Gene

The official name of this gene is “Parkinson disease (autosomal recessive, early onset) 7.”PARK7 Gene provides informations to produce DJ-1 protein ,Studies indicate that this protein has several functions like positve regualtor of androgen receptor transcription.The DJ-1 protein helps to protect brain cells (especially neurons)from oxidative stress.Oxidative stress ocurs when unstable molecules called free radicals accumulate to levels that damage or kill cell additionaly it also function as a Chaperone molecule that helps fold newly produced proteins into the proper 3-dimensional shape and helps refold damaged proteins.Researchers also suggest that the DJ-1 protein may play a role in activities that produce and process RNA, a chemical cousin of DNA.

Location :PARK7 gene is present chromosome 1 and coded from 7944380 to 7967926 region ,the cytogenetic location is 1p36.23 ,The gene size is 23547 bp with 7 exons

Disease:

Parkinson disease is caused by mutation in PARK7 gene,reseachers had identified more than 10 PARK7 mutations that cause early-onset Parkinson disease,In some cases large portion of PARK& gene is deleted and no product is produced (functional DJ-1 Protein),other mutations creates an altered protein which doesn not function properly

Understanding Parkinson's Disease


Mode of action:

Some researchers suggest PARK7 mutations distrupt teh proteins chaperone function which leads to a toxic buildup of misfold or damaged proteins and eventually to cell death.Another possibility is that PARK7 mutations impair the protein's ability to protect cells from destructive oxidative stress. Nerve cells that make the chemical messenger dopamine are particularly vulnerable to oxidative stress. With diminished protection, free radicals may cause enough damage to kill these nerve cells. Loss of dopamine-producing nerve cells is a characteristic feature of Parkinson disease.

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MUTYH Gene

Definition: mutY homolog (E. coli)

Official Symbol:MUTYH

Chromosome:1

Location : 1p34.3-p32.1

Gene Size: 11229 bp complement(45567501..45578729)


No Exons:16

Description:
MUTYH gene encodes a MYH glycosylase which is involved in oxidative DNA damage repair,The enzyme corrects mistakes in DNA ,which occur during DNA replication (during cell division),During cell division Guanine(G) sometimes becomes altered by oxygen and gets paired with Adenine(A),M instead of cytosine (C) MYH glycosylase fixes this mistake so mutations do not accumulate in the DNA and lead to tumor formation,This type of repair is known as base excision repair.



Disease :
familial adenomatous polyposis - caused by mutations in the MUTYH gene

Mutations in the MUTYH gene cause an autosomal recessive form of familial adenomatous polyposis (also called MYH-associated polyposis). Mutations in this gene affect the ability of cells to correct mistakes made during DNA replication. In individuals who have autosomal recessive familial adenomatous polyposis, both copies of the MUTYH gene in each cell are mutated. Most mutations in this gene result in the production of a nonfunctional or low-functioning MYH glycosylase. When base excision repair in the cell is impaired, mutations in other genes build up, leading to cell overgrowth and possibly tumor formation. Two mutations that change the sequence of the building blocks of proteins (amino acids) in MYH glycosylase are common in people of European descent. One mutation replaces the amino acid tyrosine with the amino acid cysteine at position 165 (written as Tyr165Cys or Y165C). The other mutation switches the amino acid glycine with the amino acid aspartic acid at position 382 (written as Gly382Asp or G382D).

MTR Gene

Definition:5-methyltetrahydrofolate-homocysteine methyltransferase

Official Symbol:MTR

 Chromosome:1


Gene Size: 105245 bp   235025341..235130585


No Exons:33

 Location : 1q43

Description:

MTR gene provides information for making an enzyme called methionine synthase.This enzyme, also known as cobalamin-dependent methionine synthase, catalyzes the final step in methionine biosynthesis

Disease :

Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency complementation group G,and Homocystinuria  Disease.In this disease more than 15 mutations in the MTR gene have been identified in people with homocystinuria. Many of these mutations lead to the production of an abnormally small, nonfunctional version of methionine synthase. Other mutations change single amino acids in the enzyme, which disrupts the enzyme's activity. For example, one of the most common mutations replaces the amino acid proline with the amino acid leucine at position 1173 (written as Pro1173Leu or P1173L). Without functional methionine synthase, homocysteine cannot be converted to methionine. As a result, homocysteine builds up in the bloodstream and methionine is depleted. Some of the excess homocysteine is excreted in urine. Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.

MTHFR Gene

Definition:5,10-methylenetetrahydrofolate reductase (NADPH)

Official Symbol:MTHFR

Chromosome:1


Gene Size: 20329 bp complement(11768374..11788702)


No Exons:12

Location : 1p36.3



Description:

MTHFR gene codes for an enzyme called methylenetetrahydrofolate reductase,which plays vital role in amino acid processing and protein building blocks ,Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine

Disease :

Mutations in the gene MTHFR causes disease called Homocystinuria,Homocystinuria, also known as Cystathionine beta synthase deficiency, is an inherited disorder of the metabolism of the amino acid methionine, often involving cystathionine beta synthase. It is an inherited autosomal recessive trait, About 24 mutation in MTHFR gene have been identified in people with homocystinuria,Most of these mutaions are single amino acids in methylenetetrahydrofolate reductase.These substitutions disrupt the function of the enzyme, and may inactivate it completely,Without methylenetetrahydrofolate reductase, homocysteine cannot be converted to methionine. As a result, homocysteine builds up in the bloodstream and methionine is depleted. Some of the excess homocysteine is excreted in urine. Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.

Homocystinuria, What is it?

MPZ - Myelin protein zero Gene

Definition:Myelin protein zero

Official Symbol:MPZ

Chromosome:1


Gene Size: 5227 bp (159541151..159546377)



No Exons:6


Location : 1q23.3




Description:

MPZ gene codes for making a protein called myelin protein zero, it is found abundant in the myelin sheath, the covering that protects nerves and promotes the efficient transmission of nerve impulses, Schwann cells are the only cells that produces myelin protein zero, This protein is required for the proper formation and maintenance of myelin, it acts like a molecular glue (adhesion molecule) and plays a role in tightly packing the myelin.

Disease:

Mutations in MPZ gene causes disease like Autosomal dominant form of Charcot-Marie-Tooth disease type 1 and other polyneuropathies, More than 100 mutations in MPZ gene causes a form of Charcot-Marie-tooth known as type 1B,These mutations alter the extracellular domain by replacing one of the building blocks (amino acids) in the myelin protein zero with incorrect amino acid, the altered myelin protein zero probably cannot interact properly with other myelin components, which disrupts the formation and maintenance of the myelin sheath, As a result, peripheral nerve cells cannot activate muscles used for movement or relay information from sensory cells back to the brain, causing the signs and symptoms of type 1B Charcot-Marie-Tooth disease.

MFN2 Mitofusin Gene

Definition:Mitofusin 2

Official Symbol:MFN2

Chromosome:1
Gene Size: 33197 bp (11962956..11996152)



No Exons:19


Location : 1p36.22

Description:This gene codes for a protein called mitofusin 2,This protein helps to determine the shape and structure of mitochondria during fission and fusion,This protein is involved in the regulation of vascular smooth muscle cell proliferation, and it may play a role in the pathophysiology of obesity

Disease :

Mutations in MFN2 gene cause disease like Charcot-Marie-Tooth disease (CMT disease)and Hereditary motor and sensory neuropathy VI,

In Charcot-Marie-Tooth disease Researchers have identified more than 30 MFN2 mutations,Almost all these mutations replace one of the protein building blocks in mitofusin 2 with an incorrect amino acid,As a result the mitofusin 2 protein are altered in critical region and cannot function properly,

Recent research showed that the mutated MFN2 causes mitochondria to form large clusters. In nerve cells these large clusters of mitochondria failed to travel down the axon towards the synapses. It is suggested these mitochondria clots make the synapses fail, resulting in CMT disease

LMNA Gene

Definition:Lamin A/C


Official Symbol:LMNA

Chromosome:1


Location : 1q21.2-q21.3

Gene Size: 25418 bp (154351085..154376502)


No Exons:12


Description:

The LMNA gene provides instructions for making several slightly different proteins called lamins. The two major proteins produced from this gene, lamin A and lamin C, are made in most of the body's cells. These proteins have a nearly identical sequence of protein building blocks (amino acids). The small difference in the sequence makes lamin A longer than lamin C.The nuclear lamina consists of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Through alternate splicing, this gene encodes three type A lamin isoforms. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy,

Disease :

Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome

Hutchinson-Gilford progeria syndrome

Mutation in the LMNA gene has been found in most patients with Hutchinson-Gilford progeria syndrome The G608G mutation in exon 11 of the LMNA gene is present in all individuals with HGPS,mutation changes a single DNA building block (nucleotide) in the gene. Specifically, the mutation replaces the nucleotide cytosine with the nucleotide thymine at position, This mutation is also sometimes noted as Gly608Gly or G608G, which refers to the position in the lamin A protein affected by the mutation. The C1824T mutation leads to an abnormal version of the lamin A protein called progerin, which is missing 50 amino acids near one end. The location of this mutation does not affect the production of lamin C. Other mutations in the LMNA gene have been identified in a small number of people with the features of Hutchinson-Gilford progeria syndrome.

The mutations responsible for this disorder result in an abnormal version of lamin A that cannot be processed correctly within the cell. When the altered protein is incorporated into the lamina, it can disrupt the shape of the nuclear envelope. Over time, a buildup of this altered protein appears to damage the structure and function of the nucleus, making cells more likely to die prematurely. Researchers are working to determine how these changes lead to the signs and symptoms of Hutchinson-Gilford progeria syndrome.

KIF1B Gene

Definition:Kinesin family member 1B


Official Symbol:KIF1B

 Chromosome:1


 Location : 1p36.2


Gene Size: 170825 bp (REGION: 10193418..10364242)


No Exons:47

Description:

This gene encodes a motor protein that transports mitochondria and synaptic vesicle precursors.These proteins are essential for the transport of materials within cells. Kinesin proteins function like freight trains that transport cargo, and their structure is suited for this cargo-carrying function. One part of the protein, called the motor domain, powers the protein and its cargo along a track-like system made from structures called microtubules. Another part of the kinesin protein, which varies among family members, binds to specific materials for transport.

Kinesin Transport Protein

Disease :

Mutations in this gene cause a, type 2A1.One KIF1B gene mutation has been detected in some patients with a form of Charcot-Marie-Tooth disease known as type 2A. The mutation changes one of the protein building blocks (amino acids) in the motor domain of kinesin family member 1B. Specifically, the amino acid glutamine is replaced by the amino acid leucine at protein position 98 (written as Gln98Leu). Although the effect of this mutation is not fully understood, the motor function of the protein and the transport of synaptic vesicles are probably disrupted. Lowered levels of synaptic vesicles at nerve endings could impair the transmission of nerve impulses, causing the symptoms of type 2A Charcot-Marie-Tooth disease.

KCNQ4 Gene

Definition: Potassium voltage-gated channel, KQT-like subfamily, member 4

Official Symbol:KCNQ4

 Chromosome:1

 Location : 1p34

Gene Size: 54677 bp (41022271..41076947)


No Exons:14


Description:

The protein encoded by this gene forms a potassium channel that is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of the cochlea. The current generated by this channel is inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene,Potassium channels made with the KCNQ4 protein are found in the inner ear and along part of the nerve pathway from the ear to the brain (auditory pathway). KCNQ4 potassium channels are also found in small numbers in the heart and some muscles.

Disease :

Defects in this gene are a cause of nonsyndromic sensorineural deafness type 2 (DFNA2), an autosomal dominant form of progressive hearing loss. Two transcript variants encoding different isoforms have been found for this gene.

Nonsyndromic deafness - caused by mutations in the KCNQ4 gene

    Several KCNQ4 mutations have been reported in individuals with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNA2. Most KCNQ4 mutations change one of the building blocks (amino acids) used to make the KCNQ4 protein. Nearly all of these changes affect the region of the protein that forms the pore or channel opening. As a result, the channel does not function properly and normal potassium ion levels may be disturbed. Two mutations delete part of the KCNQ4 gene, which results in an abnormally small KCNQ4 protein that cannot form functional channels. It is unclear whether deafness results from disturbed potassium levels within the inner ear, alterations in the auditory pathway, or both.

IRF6 Gene

Definition:Interferon regulatory factor 6


Official Symbol:IRF6


 Chromosome:1


 Location : 1q32.3-q41


Gene Size: 18218 bp complement(208027885..208046102)


No Exons: 9

Description:

This gene encodes a member of the interferon regulatory transcription factor (IRF) family. Family members share a highly-conserved N-terminal helix-turn-helix DNA-binding domain and a less conserved C-terminal protein-binding domain.

Disease :

Mutations in this gene can cause van der Woude syndrome and popliteal pterygium syndrome. This protein is involved in palate formation.A shortage of the IRF6 protein affects the development and maturation of tissues in the skull and face. These abnormalities underlie the signs and symptoms of van der Woude syndrome, including cleft lip, cleft palate (an opening in the roof of the mouth), and pits or mounds in the lower lip.

Popliteal Pterygium syndrome

Mutations in the IRF6 gene that cause popliteal pterygium syndrome may change the transcription factor's effects on the activity of certain genes. This affects the development and maturation of tissues in the face, skin, and genitals, resulting in the facial and genital abnormalities, skin webbing, and fusion of the fingers or toes (syndactyly) seen in popliteal pterygium syndrome.

RNASEL Gene

Defintion:Ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent)

Official Symbol:RNASEL

 Chromosome:1


 Location : 1q25

Gene Size: 13337 BP complement(155654005..155667341)



No Exons: 6


Description:

This gene encodes a component of the interferon-regulated 2-5A system that functions in the antiviral and antiproliferative roles of interferons. Mutations in this gene have been associated with predisposition to prostate cancer and this gene is a candidate for the hereditary prostate cancer 1 (HPC1) allele. [provided by RefSeq]

Disease :

RNase L is part of the body's innate immune defense, namely the antiviral state of the cell. When a cell is in the antiviral state, it is highly resistant to viral attacks and is also ready to undergo apoptosis upon successful viral infection. Degradation of all RNA within the cell (which usually occurs with cessation of translation activity caused by protein kinase R is the cell's last stand against a virus before it attempts apoptosis.

Prostate Cancer - Radical Prostatectomy

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.

ESPN Gene

Definition:

The official name of ESPN is "espin",ESPN is the official Gene symbol,it is also knwon has DFNB36; LP2654; DKFZp434A196; DKFZp434G2126

Chromosome:1

Position:1p36.31; 1p36.31-p36.11

Gene Size: 36157 bp (6407435 to 6443591


No of  Exons: 13

Description:

ESPN  provides instruction for making a protein called espin.This protein is active ear where it plays important role in normal hearing and balance,it is believed to bind  with actin a protein that is important for cell movement and shape,it probably involved in the growth and maintiance of hair like projections called strereocilia,Espin may also play a role in other types of sensory cells. Some studies suggest that this protein is present in taste receptor cells, cells involved in recognizing smells, and Merkel cells in the skin, which are associated with the sense of touch. In these cells, espin is located in small, fingerlike structures called microvilli that project from the cell surface. Like stereocilia in the inner ear, microvilli contain a large amount of actin.

Disease :

Mutations in ESPN gene causes nonsyndromic deafness(hearing loss without related signs and symptoms affecting other parts of the body) called DFNB36.Several  mutations in ESPN gene  cause an autosomal recessive form of nonsyndromic deafness that includes problems with balance. Autosomal recessive inheritance means that two copies of the gene in each cell are altered. These genetic changes delete a small amount of DNA from critical regions of the ESPN gene. Researchers believe that these genetic changes may prevent the production of espin or lead to an abnormally small, nonfunctional version of the protein that cannot bind to actin. A loss of espin function likely disrupts the development, structure, and organization of stereocilia, leading to hearing loss and balance problems.

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)