VPS13B
VPS13B also known as vacuolar protein sorting-associated protein 13B is a protein that in humans is encoded by the VPS13B gene. It is a giant protein associated with the Golgi apparatus that is believed to be involved in post Golgi apparatus sorting and trafficking. Mutations in the human VPS13B gene cause Cohen syndrome. VPS13B gene is also referred to as CHS1, COH1, KIAA0532, and DKFZp313I0811. Cytogenetic location of the human VPS13B gene is 8q22, which is the long arm of chromosome eight at position 22.2. There has been various splice variants encoding isoforms identified. The canonical form of  the expressed protein encoded by the human VPS13B gene has 3997 amino acids. Gene. The VPS13B gene is located on chromosome 8q22, and which deletions in this chromosome are associated with Cohen Syndrome, which is why this gene is alternatively called COH1. The gene is made up of 66 exons, 4 of which are alternative. The pattern of alternative splicing in the VS13B gene is complex in the analyzed regions including exons 28B and 28. This eventually causes 4 termination codons and 3 alternatively spliced forms to be in use. Exon 2 is where its translation start codon occurs. VPS13B  is a large gene; It spans a genomic DNA sequence region of about 864 kilobase pairs, or 846,000 base pairs. The VPS13B gene is widely expressed, especially in prostate, testis, ovary, and colon with transcripts of about 12 to 14 kilobase pairs. It is also expressed in fetal brain, liver, and kidney, with transcripts of about 2.0 to 5.0 kilobase pairs. Expression in the adult brain is very minimal. Variants 1A and 2A are the principle variants of the gene that encodes a 4,022 and 39,997 amino acid protein, respectively. 2 Alu repeat sequences are present in the three prime  untranslated region. Nomenclature. The VPS13B gene is also known as: Function. Proteins produced from the VPS13B gene are part of the Golgi apparatus. They are also responsible for sorting and transporting of proteins inside of the cell. The VPS13B protein is important because it plays an important role in the function of normal growth, the development of neurons, and the development of adipocytes. This protein may also play a role in the development of the function for eyes, the hematological system, the central nervous system, and in the storage and distribution of fats in the body. The VPS13B is found  at locus 8q22.2. This means that the VPS13B gene is located on chromosome 8 at position 22.2 on the long q arm at 8q22.2. The VPS13B protein is composed of 4,022 amino acids and might have a total of ten trans-membrane domains and a complex pattern of functional motifs. Presently, the VPS13B gene is recognized as a protein-coding gene that produces the VPS13B protein. The VPS13B protein has been associated with the Golgi apparatus and intracellular processes such as protein modification, protein organization, and protein distribution. It has also been speculated that the VPS13B protein may influence the  development of certain somatic cells and body systems, and may be involved in the storing and allocation of fats in humans. Mutations in the VPS13B gene can result in the abnormal function of the VPS13B protein. Mutations within the gene have been linked as a potential factor in Cohen Syndrome and autism. In Cohen syndrome, it is thought that deletion mutations in the gene alter the shape of the VPS13B protein, resulting in a shorter, nonfunctioning protein. Altered VPS13B protein is then unable to function properly due to these genetic changes, thus resulting in an obstruction of regular processes. Studies  have also linked mutations in the VPS13B gene to osteoporosis. An association between an increase of the VPS13B copy number variants and a lower bone mineral density in adults has been found. Still, the normal, definitive function of the VPS13B gene is unknown, as are the specific implications of its mutated forms. Clinical significance. Over 150 types of different mutations in the "VPS13B" gene have been identified in individuals diagnosed with Cohen syndrome. A deletion in the "VPS13B" gene causes a premature stop signal in the instructions for making the VPS13B protein, causing the protein to become abnormally short and  nonfunctional. When this happens, the nonfunctional protein causes the Golgi apparatus not to work properly and stops normal glycosylation. Cohen syndrome. COH1 depletion in HeLa cells by RNA interference disrupts normal Golgi organization. Deletions in this gene is a cause of autosomal recessive Cohen syndrome. Fibroblasts from Cohen syndrome patients also have abnormal Golgi. Cohen syndrome patients have been shown to have defective protein glycosylation, which is a major function of the Golgi, thus supporting the suggestion that Golgi dysfunction contributes to Cohen syndrome pathology. Cohen syndrome is a very rare inherited genetic condition, that has been diagnosed in almost  one thousand people worldwide. It occurs when there is a mutation in one’s VPS13B gene. This disorder causes a variety of symptoms that never ease. Microcephaly, hypotonia, worsening eyesight, retinal dystrophy, delayed puberty, hyper mobility, and obesity are just a few examples. People with this syndrome have distinct facial features that differ from the normal view of one. They have bulging noses, unusually shaped eyes, very thick hair, narrow hands and feet, almond like eyes, and very long, thin fingers. The symptoms of Cohen syndrome begin to show at a very young age. At birth, newborns can show no  symptoms at all, but once they start to develop their facial characteristics, it will be noticeable. It then begins with failure to thrive in infants and children, from there it is when all of the developmental delays start to show: microcephaly, retinochorodial dystrophy, psychomotor retardation, high myopia, neutropenia, joint hyper mobility and the distinct facial features start forming. Then, during the teenage and adolescent years, short stature and obesity start to become concerns. Almost thirty percent of people with this syndrome are non verbal and illiterate. In many instances where speech delay is prominent in this syndrome, aphthous ulcers are  all inside the mouth causing a lot of pain to the affected individual. Over time, many Cohen syndrome affected people start to lose their eyesight by the mere age of thirty. Although Cohen syndrome does not decrease one’s life expectancy, but it reduces their quality of life due to being unable to speak and/or see. Patients with this syndrome are known to also suffer from seizures, narrow hands and feet, and growth hormone deficiencies. Cohen syndrome is an autosomal recessive disorder that is characterized by mainly facial dysmorphism, microcephaly, joint laxity and intermittent neutropenia. Cohen syndrome is inherited in  an autosomal recessive manner, which means there is a 50 percent chance of being a carrier. Children of people with this syndrome are carriers for the syndrome. Seventy-five percent of individuals with Cohen syndrome, in the Finnish population, have a mutation in both copies of the gene. Mutations in the gene VPS13B only occur in a small number of families, outside of Finnish and Amish groups. Neutropenia. Another disease that the VPS13B gene contributes to is neutropenia. The disease is that the person will have a low concentration of neutrophils. Neutrophils is a type of white blood cell. Which  it causes the person to be able to catch other infections and disease easier. Even though it is a genetic disease it can be cause by certain medications and sometimes your bone marrow. Sutton disease 2. Sutton disease is a chronic inflammatory disease that happens in a person mouth. It creates painful ulcers in the mouth area. The sours can be different size and different pain levels. Another name for this disease that it is commonly known for is canker sores. Ewing sarcoma. Ewing sarcoma is a cancers tumor that happens in your bones or soft tissues. Examples for this  cartilage or nerves. It usually shows up in children, teens and young adults. There are other diseases that are similar to the Ewing sarcoma but this one is the only one that has the VPS13B gene. Microcephaly. Microcephaly is a medical condition which the head is misshaped and is smaller than the normal size head shape. The reason it occurs is that will the fetus was in the womb its head stopped forming or the brain stop forming. It effects the head and brain shaped. Even when this occurs the person will be normal, and it does not affect them , but this is on occasion. Most of the time when this happens, they have problems with seizures, development delays, problems with movement and also balance, hard time eating, and hearing loss and losing vision can occur. Other. Syndromic autism is also associated with this gene, as well as intellectual disability.