View source for VPS13B

{{protein
| Name = vacuolar protein sorting 13B (yeast)
| caption = 
| image = 
| width = 
| HGNCid = 2183
| Symbol = VPS13B
| AltSymbols = CHS1, COH1
| EntrezGene = 157680
| OMIM = 607817
| RefSeq = NM_184042
| UniProt = Q7Z7G8
| PDB = 
| ECnumber = 
| Chromosome = 8
| Arm = q
| Band = 22
| LocusSupplementaryData = -q23
}}
'''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.<ref>{{cite web|url=http://www.ebi.ac.uk/interpro/entry/IPR039782|title=Vacuolar protein sorting-associated protein 13B (IPR039782) | work = InterPro | publisher = EMBL-EBI |access-date=2018-11-11}}</ref>  Mutations in the human VPS13B gene cause [[Cohen syndrome]].

VPS13B gene is also referred to as CHS1, COH1, KIAA0532,<ref name=":0">{{cite web |url=https://www.ncbi.nlm.nih.gov/gene/157680 |title=VPS13B vacuolar protein sorting 13 homolog B [Homo sapiens (human)] - Gene - NCBI | work = Entrez Gene | publisher = National Center for Biotechnology Information  |access-date=2018-11-07}}</ref> and DKFZp313I0811.<ref name = "SG_VPS13B">{{cite web |url=https://gene.sfari.org/database/human-gene/VPS13B |title=Gene: VPS13B | work = SFARI Gene |access-date=2018-11-08}}</ref> 

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]].<ref name=":0" />

== Gene ==
The VPS13B gene is located on chromosome 8q22, and which deletions in this chromosome are associated with [[Cohen syndrome|Cohen Syndrome]], which is why this gene is alternatively called COH1.<ref name="Deng_2010">{{cite journal | vauthors = Deng FY, Zhao LJ, Pei YF, Sha BY, Liu XG, Yan H, Wang L, Yang TL, Recker RR, Papasian CJ, Deng HW | title = Genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians | journal = Osteoporosis International : a Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA | volume = 21 | issue = 4 | pages = 579–87 | date = April 2010 | pmid = 19680589 | pmc = 2924432 | doi = 10.1007/s00198-009-0998-7 }}</ref> The gene is made up of 66 [[Exon|exons]], 4 of which are alternative.<ref name=":1">{{cite journal | vauthors = Velayos-Baeza A, Vettori A, Copley RR, Dobson-Stone C, Monaco AP | title = Analysis of the human VPS13 gene family | journal = Genomics | volume = 84 | issue = 3 | pages = 536–49 | date = September 2004 | pmid = 15498460 | doi = 10.1016/j.ygeno.2004.04.012 }}</ref> 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 Codon|termination codons]] and 3 [[Alternative splicing|alternatively spliced]] forms to be in use.<ref name="pmid12730828">{{cite journal | vauthors = Kolehmainen J, Black GC, Saarinen A, Chandler K, Clayton-Smith J, Träskelin AL, Perveen R, Kivitie-Kallio S, Norio R, Warburg M, Fryns JP, de la Chapelle A, Lehesjoki AE | display-authors = 6 | title = Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport | journal = American Journal of Human Genetics | volume = 72 | issue = 6 | pages = 1359–69 | date = June 2003 | pmid = 12730828 | pmc = 1180298 | doi =  }}</ref> Exon 2 is where its translation [[start codon]] occurs.<ref name=":1" /> VPS13B is a large gene; It spans a genomic DNA sequence region of about 864 kilobase pairs, or 846,000 base pairs.<ref name=":1" /> 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.<ref>{{cite web|url=http://www.cags.org.ae/ctga/details.aspx?id=700|title=CTGA DetailsCentre for Arab Genomic Studies|last=|first=|date=2018|website=Centre for Arab Genomic Studies }}</ref> Variants 1A and 2A are the principle variants of the gene that encodes a 4,022 and 39,997 amino acid protein, respectively.<ref name="Deng_2010" /> 2 Alu repeat sequences are present in the three prime untranslated region.<ref>{{cite web |url= http://www.cags.org.ae/pdf/607817.pdf |title=COH1 Gene |last=Tadmouri |first=Ghazi | name-list-format = vanc |date=2005 |website=Centre for Arab Genomic Studies }}</ref>

== Nomenclature ==

The VPS13B gene is also known as:<ref name=":4">{{cite web|url=https://ghr.nlm.nih.gov/gene/VPS13B#resources|title=VPS13B gene|last=Reference|first=Genetics Home|website=Genetics Home Reference|language=en|access-date=2018-11-11}}</ref>

* CHS1<ref name=":4" />
* COH1<ref name=":4" />
* Cohen syndrome 1<ref name=":4" />
* DKFZp313I0811<ref name=":4" />
* KIAA0532<ref name=":4" />
* vacuolar protein sorting 13 homolog B (yeast)<ref name=":4" />
* vacuolar protein sorting 13B<ref name=":4" />
* VP13B_HUMAN<ref name=":4" />

== Function ==

Proteins produced from the VPS13B gene area part of the [[Golgi apparatus]].<ref name=":4" /> They are also responsible for sorting and transporting of proteins inside of the cell.<ref name=":4" /> 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.<ref name=":4" /> 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.<ref>{{cite web|url=https://genecards.weizmann.ac.il/v3/cgi-bin/carddisp.pl?gene=VPS13B |title=VPS13B Human Gene | work = GeneCards  |access-date=2018-11-11}}</ref> The VPS13B is found at locus 8q22.2.<ref name=":4" /> This means that the VPS13B gene is located on chromosome 8 at position 22.2 on the long q arm at 8q22.2.<ref name=":4" /> 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.<ref>{{cite web|url=https://www.genedx.com/wp-content/uploads/crm_docs/info_sheet_coh.pdf|title=VPS13B (COH1) Gene Analysis in Cohen Syndrome |date=December 2016|website=GeneDx |access-date=November 4, 2018}}</ref>

Presently, the VPS13B gene is recognized as a protein-coding gene that produces the VPS13B protein.<ref>{{cite web|url=http://grch37.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000132549;r=8:100025494-100889808|title=Gene: VPS13B (ENSG00000132549) Homo sapiens | work = GRCh37 Archive browser 94 |access-date=2018-11-09}}</ref> The VPS13B protein has been associated with the Golgi apparatus and intracellular processes such as [[Post-translational modification|protein modification]], protein organization, and protein distribution.<ref name="ghr_VPS13B" /> It has also been speculated that the VPS13B protein may influence the development of certain [[Somatic cell|somatic cells]] and body systems, and may be involved in the storing and allocation of fats in humans.<ref name=":0" /><ref name="ghr_VPS13B" />

[[Mutation|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|Cohen Syndrome]] and [[Autism|autism.]]<ref name="ghr_VPS13B" /><ref name="pmid25502226">{{cite journal | vauthors = Ionita-Laza I, Capanu M, De Rubeis S, McCallum K, Buxbaum JD | title = Identification of rare causal variants in sequence-based studies: methods and applications to VPS13B, a gene involved in Cohen syndrome and autism | journal = PLoS Genetics | volume = 10 | issue = 12 | pages = e1004729 | date = December 2014 | pmid = 25502226 | pmc = 4263785 | doi = 10.1371/journal.pgen.1004729 }}</ref><ref name=":3" /><ref name="pmid23352163">{{cite journal | vauthors = Yu TW, Chahrour MH, Coulter ME, Jiralerspong S, Okamura-Ikeda K, Ataman B, Schmitz-Abe K, Harmin DA, Adli M, Malik AN, D'Gama AM, Lim ET, Sanders SJ, Mochida GH, Partlow JN, Sunu CM, Felie JM, Rodriguez J, Nasir RH, Ware J, Joseph RM, Hill RS, Kwan BY, Al-Saffar M, Mukaddes NM, Hashmi A, Balkhy S, Gascon GG, Hisama FM, LeClair E, Poduri A, Oner O, Al-Saad S, Al-Awadi SA, Bastaki L, Ben-Omran T, Teebi AS, Al-Gazali L, Eapen V, Stevens CR, Rappaport L, Gabriel SB, Markianos K, State MW, Greenberg ME, Taniguchi H, Braverman NE, Morrow EM, Walsh CA | display-authors = 6 | title = Using whole-exome sequencing to identify inherited causes of autism | journal = Neuron | volume = 77 | issue = 2 | pages = 259–73 | date = January 2013 | pmid = 23352163 | pmc = 3694430 | doi = 10.1016/j.neuron.2012.11.002 }}</ref> In Cohen syndrome, it is thought that [[Deletion (genetics)|deletion mutations]] in the gene alter the shape of the VPS13B protein, resulting in a shorter, nonfunctioning protein.<ref name="ghr_VPS13B" /><ref name=":3" /> Altered VPS13B protein is then unable to function properly due to these genetic changes, thus resulting in an obstruction of regular processes.<ref name="ghr_VPS13B" /> Studies have also linked mutations in the VPS13B gene to [[Osteoporosis|osteoporosis.]]<ref name="Deng_2010" /> An association between an increase of the VPS13B [[Copy-number variation|copy number variants]] and a lower [[Bone density|bone mineral density]] in adults has been found.<ref name="Deng_2010" /> 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.<ref name=":4" /> 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.<ref name=":4" /> When this happens, the nonfunctional protein causes the Golgi apparatus not to work properly and stops normal glycosylation.<ref name=":4" />

=== Cohen syndrome ===
{{Main|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.<ref name="pmid21865173">{{cite journal | vauthors = Seifert W, Kühnisch J, Maritzen T, Horn D, Haucke V, Hennies HC | title = Cohen syndrome-associated protein, COH1, is a novel, giant Golgi matrix protein required for Golgi integrity | journal = The Journal of Biological Chemistry | volume = 286 | issue = 43 | pages = 37665–75 | date = October 2011 | pmid = 21865173 | pmc = 3199510 | doi = 10.1074/jbc.M111.267971 }}</ref> Cohen syndrome patients have been shown to have defective protein [[glycosylation]],<ref name="pmid24334764">{{cite journal | vauthors = Duplomb L, Duvet S, Picot D, Jego G, El Chehadeh-Djebbar S, Marle N, Gigot N, Aral B, Carmignac V, Thevenon J, Lopez E, Rivière JB, Klein A, Philippe C, Droin N, Blair E, Girodon F, Donadieu J, Bellanné-Chantelot C, Delva L, Michalski JC, Solary E, Faivre L, Foulquier F, Thauvin-Robinet C | display-authors = 6 | title = Cohen syndrome is associated with major glycosylation defects | journal = Human Molecular Genetics | volume = 23 | issue = 9 | pages = 2391–9 | date = May 2014 | pmid = 24334764 | doi = 10.1093/hmg/ddt630 }}</ref> which is a major function of the Golgi, thus supporting the suggestion that Golgi dysfunction contributes to Cohen syndrome pathology.<ref name="pmid21865173"/>

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.<ref>{{cite web |url= https://ghr.nlm.nih.gov/condition/cohen-syndrome#sourcesforpage|title=Cohen syndrome |website=Genetics Home Reference |access-date=2018-11-09}}</ref>

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.<ref name = "Orphanet">{{cite web |url= https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=445&Disease_Disease_Search_diseaseGroup=Cohen-syndrome&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Cohen-syndrome&title=Cohen%20syndrome&search=Disease_Search_Simple |title=Cohen syndrome|work = Orphanet: The portal for rare diseases and orphan drugs | publisher = INSERM US14 | location = Paris, France |access-date=2018-11-10}}</ref> 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.<ref name = "Wang_1993">{{cite journal | vauthors = Wang H, Falk MJ, Wensel C, Traboulsi E | title = Cohen Syndrome | date = 1993 | pmid = 20301655 | url = http://www.ncbi.nlm.nih.gov/books/NBK1482/ | access-date = 2018-11-10 | publisher = University of Washington, Seattle | veditors =  Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A }}</ref> 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.<ref name = "Orphanet" /> Patients with this syndrome are known to also suffer from seizures, narrow hands and feet, and growth hormone deficiencies.<ref>{{OMIM|216550|Cohen Syndrome; COH1}}</ref>

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.<ref name=":3">{{cite journal | vauthors = Balikova I, Lehesjoki AE, de Ravel TJ, Thienpont B, Chandler KE, Clayton-Smith J, Träskelin AL, Fryns JP, Vermeesch JR | title = Deletions in the VPS13B (COH1) gene as a cause of Cohen syndrome | journal = Human Mutation | volume = 30 | issue = 9 | pages = E845-54 | date = September 2009 | pmid = 19533689 | doi = 10.1002/humu.21065 }}</ref> 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.<ref name="ghr_VPS13B">{{cite web| url= https://ghr.nlm.nih.gov/gene/VPS13B#normalfunction |title=VPS13B gene |work=Genetics Home Reference |access-date=2018-11-07}}</ref>

=== Neutropenia ===
Another disease that the VPS13B gene contributes to is [[neutropenia]]. The disease is that the person will have a low concentration of neutrophils.<ref name=":02">{{cite web|url=https://www.malacards.org/card/neutropenia|title=Neutropenia disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials | access-date=2018-11-11}}</ref> Neutrophils is a type of white blood cell. Which it causes the person to be able to catch other infections and disease easier.<ref name=":02" /> Even though it is a genetic disease it can be cause by certain medications and sometimes your bone marrow.<ref name=":02" />

=== Sutton disease 2 ===
[[Sutton disease]] is a chronic inflammatory disease that happens in a person mouth. It creates painful ulcers in the mouth area.<ref name=":12">{{cite web|url=https://www.malacards.org/card/sutton_disease_2|title=Sutton Disease 2 disease | work = Malacards - Research Articles, Drugs, Genes, Clinical Trials | access-date=2018-11-11}}</ref> The sours can be different size and different pain levels. Another name for this disease that it is commonly known for is canker sores.<ref name=":12" />

=== Ewing sarcoma ===
[[Ewing sarcoma]] is a cancers tumor that happens in your bones or soft tissues.<ref name=":2">{{cite web|url=https://www.malacards.org/card/ewing_sarcoma|title=Ewing Sarcoma disease | work = Malacards - Research Articles, Drugs, Genes, Clinical Trials | access-date=2018-11-11}}</ref> Examples for this cartilage or nerves.<ref name=":2" /> It usually shows up in children, teens and young adults.<ref name=":2" />  There are other diseases that are similar to the Ewing sarcoma but this one is the only one that has the VPS13B gene.<ref name=":2" />

=== Microcephaly ===
[[Microcephaly]] is a medical condition which the head is misshaped and is smaller than the normal size head shape.<ref name=":32">{{cite web|url=https://www.malacards.org/card/microcephaly|title=Microcephaly disease | work = Malacards - Research Articles, Drugs, Genes, Clinical Trials | access-date=2018-11-11}}</ref> The reason it occurs is that will the fetus was in the womb its head stopped forming or the brain stop forming.<ref name=":32" /> 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.<ref name=":32" /> 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.<ref name=":32" />

=== Other ===
Syndromic [[autism]] is also associated with this gene,<ref name = "SG_VPS13B" /> as well as [[intellectual disability]].<ref>{{cite web|url=https://databases.lovd.nl/shared/diseases/00139|title=Disease #00139 - Global Variome shared LOVD|last=Netherlands| work = Leiden Open Variation Database (LOVD) |access-date=2018-11-09}}</ref><ref>{{cite news|url=https://vector.childrenshospital.org/2013/01/inherited-autism-mutations-found-via-genomic-sequencing-in-mideast-families/|title=Inherited autism mutations found via genomic sequencing in Mideast families |date=2013-01-25|work=Vector | publisher = Boston Children’s Hospital |access-date=2018-11-09}}</ref>

== References ==
{{reflist}}

== External links ==
* [http://cohen-syndrome.org/ Cohen Syndrome association]
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cohen  GeneReviews/NCBI/NIH/UW entry on Cohen syndrome]

{{Vesicular transport proteins}}

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