USH2A gene

The official name of USH2A gene is Usher syndrome 2A (autosomal recessive, mild)..The USH2A gene provides instructions for making anan enzyme called usherin. Usherin is an important component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Usherin is found in the inner ear and the part of the eye that detects light and color (the retina). Although the function of usherin has not been well established, studies suggest that this protein is part of a larger protein complex that plays an important role in inner ear and retinal development. In these locations, the protein complex may also be involved in the function of synapses, which are junctions between nerve cells where cell-to-cell communication occurs.

Location:

USH2A gene is present in human chromosome 1 and ts coded from region 213,862,858 to 214,663,360 complement with 71 exons, the cytogenetic location 1q41.

Disease

Mutations in USH2A gene causes a form of  Usher syndrome type IIA,Usher syndrome is a condition characterized by hearing loss or deafness and progressive vision loss. The loss of vision is caused by an eye disease called retinitis pigmentosa (RP), which affects the layer of light-sensitive tissue at the back of the eye (the retina). Vision loss occurs as the light-sensing cells of the retina gradually deteriorate.Mutations change single protein building blocks (amino acids) in the usherin protein. In some cases, these mutations lead to the production of an abnormally short version of the protein or prevent the cell from making any functional usherin. Other mutations insert or delete small amounts of DNA in the USH2A gene, which probably impairs the normal function of usherin. Researchers have not determined how a missing or altered usherin protein leads to the signs and symptoms of Usher syndrome.The most common mutation in the USH2A gene is found in about 25 percent of people with Usher syndrome type IIA, particularly those from Europe, the United States, South Africa, and China. This mutation deletes a specific DNA building block, a guanine (G) nucleotide, at position 2299 in the USH2A gene (written as 2299delG). Individuals with this change, or with similar mutations in the USH2A gene, develop moderate to severe hearing loss and retinitis pigmentosa, a disorder that results in loss of vision.

UROD Gene

The official name of UROD gene is uroporphyrinogen decarboxylase.The UROD gene provides instructions for making anan enzyme called uroporphyrinogen decarboxylase. Uroporphyrinogen III decarboxylase (UroD) is a homodimeric enzyme which catalyzes the fifth step in heme biosynthesis: the elimination of carboxyl groups from the four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III.Three additional enzymes modify this product before it becomes heme. The heme molecule is then incorporated into hemoglobin and packaged into red blood cells, or it is used in the liver for the production of certain liver enzymes.

Location:

UROD gene is present in human chromosome 1 and ts coded from region 45250417 to 45253928 with 10 exons, the cytogenetic location 1p34.

Disease

Mutations in UROD gene causes a form of porphyria called porphyria cutanea tarda and hepatoerythropoietic porphyria,In porphyria cutanea tarda the mutations occur in one of the two copies of the UROD gene in each cell, which usually reduces the activity of uroporphyrinogen decarboxylase by 50 percent throughout the body.As a result, byproducts of heme production called porphyrins build up in the body, particularly in the liver. This buildup, in combination with nongenetic factors (such as alcohol, smoking, certain hormones, excess iron, and viral infections), causes this type of porphyria.

In hepatoerythropoietic porphyria Most of the mutations are unique in this type of porphyria and have not been found in porphyria cutanea tarda. Mutations that cause hepatoerythropoietic porphyria occur in both copies of the UROD gene in each cell, which reduces the activity of uroporphyrinogen decarboxylase to less than 10 percent of normal. Extremely low levels of this enzyme prevent sufficient amounts of heme from being produced. As a result, byproducts of heme production called porphyrins build up in the body, causing this type of porphyria.

SDHB Gene

The official name of SDHB gene is succinate dehydrogenase complex, subunit B, iron sulfur (Ip),The SDHB  gene provides instructions for making a protein called succinate dehydrogenase(SDH). The succinate dehydrogenase (SDH) protein complex catalyzes the oxidation of succinate (succinate + ubiquinone => fumarate + ubiquinol). The SDHB subunit is connected to the SDHA subunit on the hydrophilic, catalytic end of the SDH complex. It is also connected to the SDHC/SDHD subunits on the hydrophobic end of the complex anchored in the mitochondrial membrane. The subunit is an iron-sulfur protein with three iron-sulfur clusters. It weighs 30 kDa.The SDH complex is located on the inner membrane of the mitochondria and participates in both the Citric Acid Cycle and Respiratory chain.

SDHB acts as an intermediate in the basic SDH enzyme action:

   1. SDHA converts succinate to fumarate as part of the Citric Acid Cycle. This reaction also converts FAD to FADH2.
   2. Electrons from the FADH2 are transferred to the SDHB subunit iron clusters [2Fe-2S],[4Fe-4S],[3Fe-4S].
   3. Finally the electrons are transferred to the Ubiquinone (Q) pool via the SDHC/SDHD subunits.This function is part of the Respiratory chain.

Sporadic and familial mutations in this gene result in paragangliomas (glomus tumors)and pheochromocytoma, and support a link between mitochondrial dysfunction and tumorigenesis.

Mutations causing disease have been seen in exons 1 through 7, but not 8. As with the SDHC and SDHD genes, SDHB is a tumor suppressor gene. Note the SDHA gene is not a tumor suppressor gene.

Tumor formation generally follows the Knudson "two hit" hypothesis. The first copy of the gene is mutated in all cells, however the second copy functions normally. When the second copy mutates in a certain cell due to a random event, Loss of Heterozygosity (LOH) occurs and the SDHB protein is no longer produced. Tumor formation then becomes possible.

Given the fundamental nature of the SDH protein in all cellular function, it is not currently understood why only paraganglionic cells are affected. However, the sensitivity of these cells to oxygen levels may play a role.

PSEN2 gene

The official name of PSEN2 gene is presenilin 2 (Alzheimer disease 4),The PSEN2 gene provides instructions for making a protein called presenilin 2. Presenilin 2 helps process certain proteins that are important for transmitting biochemical signals from the cell membrane into the nucleus of the cell. In the nucleus, these signals turn on (activate) particular genes that are important for cell growth and maturation. Presenilin 2 is also involved in processing amyloid precursor protein, which is found in the brain and other tissues. Research suggests that presenilin 2 works as part of an enzyme complex that cuts amyloid precursor protein into smaller segments (peptides). One of these peptides is called soluble amyloid precursor protein (sAPP) and another is called amyloid beta peptide. Recent evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of nerve cells in both embryonic and adult brain tissue. Other functions of sAPP and amyloid beta peptide are under investigation.

Location:
PSEN gene is present in human chromosome 1 and ts coded from region 225124896 to 225150427, the cytogenetic location 1q31-q42

Disorder:
Mutations in this gene causes Alzheimer's disease 4

Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1 or PSEN2) or the amyloid precursor protein (APP).Researcher have found approxiametly 11 mutaions in PSEN gene have been shown to cause type 4 Alzheimer disease.Two of the most common PSEN2 mutations that cause type 4 Alzheimer disease change one of the building blocks (amino acids) used to make presenilin 2. One mutation replaces the amino acid asparagine with the amino acid isoleucine at position 141 (written as Asn141Ile or N141I). The other mutation changes the amino acid methionine to the amino acid valine at position 239 (written as Met239Val or M239V). These mutations appear to affect the processing of amyloid precursor protein.These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor such that, they either directly regulate gamma-secretase activity, or themselves act are protease enzymes. Two alternatively spliced transcript variants encoding different isoforms of PSEN2 have been identified.

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.

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.

New Drug Approved by FDA for Parkinson's Disease

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

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.