Health Topics

Skip navigation

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( Lock Locked padlock icon ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

You Are Here:
Home →
Genetics →
Genes →
CHMP2B gene
URL of this page: https://medlineplus.gov/genetics/gene/chmp2b/

CHMP2B gene

charged multivesicular body protein 2B

Normal Function

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).

Health Conditions Related to Genetic Changes

CHMP2B-related frontotemporal dementia

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.

More About This Health Condition

Amyotrophic lateral sclerosis

MedlinePlus Genetics provides information about Amyotrophic lateral sclerosis

More About This Health Condition

Other Names for This Gene

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

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

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. Citation on PubMed or Free article on PubMed Central
  • Lee JA, Gao FB. ESCRT, autophagy, and frontotemporal dementia. BMB Rep. 2008 Dec 31;41(12):827-32. doi: 10.5483/bmbrep.2008.41.12.827. Citation on PubMed
  • 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. doi: 10.1159/000094771. Citation on PubMed
  • 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, Sorensen 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. doi: 10.1038/ng1609. Epub 2005 Jul 24. Citation on PubMed
  • 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. Citation on PubMed or Free article on PubMed Central
  • 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. Citation on PubMed
  • 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. doi: 10.1093/hmg/ddm309. Epub 2007 Oct 22. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.