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Genetics Home Reference: your guide to understanding genetic conditions
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CHMP2B

Reviewed August 2010

What is the official name of the CHMP2B gene?

The official name of this gene is “charged multivesicular body protein 2B.”

CHMP2B is the gene's official symbol. The CHMP2B gene is also known by other names, listed below.

What is the normal function of the CHMP2B gene?

The CHMP2B gene provides instructions for making a protein called charged multivesicular body protein 2B. This protein is active in the brain, where it appears to be essential for the survival of nerve cells (neurons).

Charged multivesicular body protein 2B forms one part (subunit) of a group of proteins known as the ESCRT-III complex. This complex helps transport other proteins from the cell membrane to the interior of the cell, a process known as endocytosis. In particular, the ESCRT-III complex is involved in the endocytosis of proteins that need to be broken down (degraded) by the cell. The complex helps sort these proteins into structures called multivesicular bodies (MVBs), which deliver them to lysosomes. Lysosomes are compartments within cells that digest and recycle many different types of molecules.

Charged multivesicular body protein 2B is regulated by a segment at one end of the protein known as the C-terminal domain. This domain usually keeps the protein turned off (inactive). The inactive protein is unable to interact with other subunits of the ESCRT-III complex, which prevents the complex from forming when it is not needed. The C-terminal domain also plays an important role in disassembling the ESCRT-III complex through its interaction with a protein called vacuolar protein sorting 4 (Vps4).

Does the CHMP2B gene share characteristics with other genes?

The CHMP2B gene belongs to a family of genes called CHMP (charged multivesicular body proteins).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the CHMP2B gene related to health conditions?

CHMP2B-related frontotemporal dementia - caused by mutations in the CHMP2B gene

Several changes in the CHMP2B gene have been identified in people with frontotemporal dementia. At least two of these genetic changes are thought to be mutations that cause the disease. It is unclear whether the other genetic changes also cause disease; they may be rare variations that are unrelated to the development of frontotemporal dementia.

Most people with CHMP2B-related frontotemporal dementia are members of a single, large Danish family. Affected individuals in this family have a particular mutation, written as 532-1G>C, that changes a single DNA building block (base pair) in the CHMP2B gene. This mutation leads to the production of two abnormal versions of charged multivesicular body protein 2B, both of which are missing the C-terminal domain.

Without the C-terminal domain, charged multivesicular body protein 2B is constantly turned on (active) as part of the ESCRT-III complex. It cannot interact with Vps4, so the complex cannot be disassembled when it is no longer needed. As a result, the ESCRT-III complex builds up within cells and disrupts the transport and degradation of other proteins. These abnormalities ultimately lead to the death of neurons in the brain.

A gradual loss of neurons throughout the brain is characteristic of CHMP2B-related frontotemporal dementia. Many of the features of this disease result from neuronal death in regions near the front of the brain called the frontal and temporal lobes. The frontal lobes are involved in reasoning, planning, judgment, and problem-solving, while the temporal lobes help process hearing, speech, memory, and emotion. It is unclear why the signs and symptoms of this disease are related primarily to the frontal and temporal lobes.

Where is the CHMP2B gene located?

Cytogenetic Location: 3p11.2

Molecular Location on chromosome 3: base pairs 87,227,262 to 87,255,547

The CHMP2B gene is located on the short (p) arm of chromosome 3 at position 11.2.

The CHMP2B gene is located on the short (p) arm of chromosome 3 at position 11.2.

More precisely, the CHMP2B gene is located from base pair 87,227,262 to base pair 87,255,547 on chromosome 3.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about CHMP2B?

You and your healthcare professional may find the following resources about CHMP2B helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the CHMP2B gene or gene products?

  • CHM2B_HUMAN
  • CHMP2.5
  • CHMP family, member 2B
  • chromatin modifying protein 2B
  • DMT1
  • hVps2-2
  • vacuolar protein sorting-associated protein 2-2
  • VPS2-2
  • VPS2B
  • VPS2 homolog B

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding CHMP2B?

base pair ; cell ; cell membrane ; chromatin ; degradation ; dementia ; DNA ; domain ; endocytosis ; endosomes ; gene ; mutation ; protein ; subunit ; ubiquitin

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Ferrari R, Kapogiannis D, Huey ED, Grafman J, Hardy J, Momeni P. Novel missense mutation in charged multivesicular body protein 2B in a patient with frontotemporal dementia. Alzheimer Dis Assoc Disord. 2010 Oct-Dec;24(4):397-401. doi: 10.1097/WAD.0b013e3181df20c7. (http://www.ncbi.nlm.nih.gov/pubmed/20592581?dopt=Abstract)
  • Lee JA, Gao FB. ESCRT, autophagy, and frontotemporal dementia. BMB Rep. 2008 Dec 31;41(12):827-32. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19123971?dopt=Abstract)
  • Momeni P, Rogaeva E, Van Deerlin V, Yuan W, Grafman J, Tierney M, Huey E, Bell J, Morris CM, Kalaria RN, van Rensburg SJ, Niehaus D, Potocnik F, Kawarai T, Salehi-Rad S, Sato C, St George-Hyslop P, Hardy J. Genetic variability in CHMP2B and frontotemporal dementia. Neurodegener Dis. 2006;3(3):129-33. (http://www.ncbi.nlm.nih.gov/pubmed/16954699?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/25978)
  • Skibinski G, Parkinson NJ, Brown JM, Chakrabarti L, Lloyd SL, Hummerich H, Nielsen JE, Hodges JR, Spillantini MG, Thusgaard T, Brandner S, Brun A, Rossor MN, Gade A, Johannsen P, Sørensen SA, Gydesen S, Fisher EM, Collinge J. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat Genet. 2005 Aug;37(8):806-8. Epub 2005 Jul 24. (http://www.ncbi.nlm.nih.gov/pubmed/16041373?dopt=Abstract)
  • Urwin H, Authier A, Nielsen JE, Metcalf D, Powell C, Froud K, Malcolm DS, Holm I, Johannsen P, Brown J, Fisher EM, van der Zee J, Bruyland M; FReJA Consortium, Van Broeckhoven C, Collinge J, Brandner S, Futter C, Isaacs AM. Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations. Hum Mol Genet. 2010 Jun 1;19(11):2228-38. doi: 10.1093/hmg/ddq100. Epub 2010 Mar 10. (http://www.ncbi.nlm.nih.gov/pubmed/20223751?dopt=Abstract)
  • Urwin H, Ghazi-Noori S, Collinge J, Isaacs A. The role of CHMP2B in frontotemporal dementia. Biochem Soc Trans. 2009 Feb;37(Pt 1):208-12. doi: 10.1042/BST0370208. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19143633?dopt=Abstract)
  • van der Zee J, Urwin H, Engelborghs S, Bruyland M, Vandenberghe R, Dermaut B, De Pooter T, Peeters K, Santens P, De Deyn PP, Fisher EM, Collinge J, Isaacs AM, Van Broeckhoven C. CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro. Hum Mol Genet. 2008 Jan 15;17(2):313-22. Epub 2007 Oct 22. (http://www.ncbi.nlm.nih.gov/pubmed/17956895?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2010
Published: July 21, 2014