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CHMP2B gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

CHMP2B gene

The CHMP2B gene is essential for the survival of nerve cells, and mutations are linked to frontotemporal dementia.

Normal Function

The CHMP2B gene provides instructions for making the charged multivesicular body protein 2B, which is active in the brain and essential for the survival of neurons. This protein forms a subunit of the ESCRT-III complex, which helps transport proteins from the cell membrane to the interior of the cell for degradation, a process known as endocytosis.

The protein is regulated by a segment known as the C-terminal domain, which keeps the protein inactive when not needed. This domain also interacts with a protein called vacuolar protein sorting 4 (Vps4) to disassemble the ESCRT-III complex once its task is complete.

Health Conditions Related to Genetic Changes

CHMP2B-related frontotemporal dementia

Changes in the CHMP2B gene have been identified in people with frontotemporal dementia. A specific mutation, 532-1G>C, leads to the production of abnormal proteins missing the C-terminal domain. Without this domain, the protein remains constantly active and cannot interact with Vps4, preventing the ESCRT-III complex from disassembling.

The resulting buildup of the ESCRT-III complex disrupts the transport and degradation of other proteins, ultimately leading to the death of neurons. This neuronal loss typically occurs in the frontal and temporal lobes of the brain, which are responsible for reasoning, planning, judgment, problem-solving, hearing, speech, memory, and emotion.

Amyotrophic lateral sclerosis

The CHMP2B gene is also associated with amyotrophic lateral sclerosis.

Genomic Location

The CHMP2B gene is found on chromosome 3.

Frequently Asked Questions

Symptoms most commonly emerge between the ages of 45 and 65. The earliest signs are typically subtle changes in personality, social judgment, and emotional regulation, including profound apathy, social disinhibition, loss of empathy, and executive dysfunction (such as an inability to plan or organize tasks). As the disease progresses, patients develop language difficulties (primary progressive aphasia), hyperorality, restlessness, and eventually motor symptoms or parkinsonism.
CHMP2B encodes a subunit of the ESCRT-III complex, which is vital for the endosomal-lysosomal pathway that clears cellular debris and damaged proteins through endocytosis and autophagy. Mutations in CHMP2B produce a truncated protein lacking its normal regulatory C-terminal domain, locking the ESCRT-III complex in a constitutively active state that cannot properly disassemble. This arrest impairs the fusion of autophagosomes with lysosomes, causing an accumulation of toxic protein waste and endosomal swelling that ultimately triggers neuronal death in the frontal and temporal lobes.
lthough CHMP2B mutations were initially characterized in frontotemporal dementia (specifically FTD-3), pathogenic variants have also been identified in patients presenting with classical amyotrophic lateral sclerosis (ALS) or mixed FTD-ALS phenotypes. Because motor neurons possess long axons that rely heavily on efficient endosomal sorting and autophagic clearance to remove damaged organelles, the disruption of the ESCRT-III complex caused by CHMP2B defects can lead to progressive degeneration of upper and lower motor neurons.
CHMP2B-associated frontotemporal dementia is inherited in an autosomal dominant pattern with very high penetrance, meaning an affected individual has a 50% chance of passing the altered gene to each child, and nearly all carriers develop symptoms if they live to middle age. Asymptomatic adult family members seeking predictive testing should participate in formal pre-test genetic counseling to evaluate the personal, psychological, legal, and financial impacts of testing, particularly given the current lack of curative or preventative treatments.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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