CHMP2B

CHMP2B

Pathway Diagram

```mermaid
flowchart TD
CHMP2B["CHMP2B<br/>Charged Multivesicular<br/>Body Protein 2B"]

ESCRT["ESCRT-III<br/>Complex"]
CHMP2A["CHMP2A<br/>Related Protein"]
VCP["VCP/Valosin<br/>Containing Protein"]

Autophagy["Autophagy<br/>Dysfunction"]
Endosome["Endosomal<br/>Trafficking"]
ProteinAgg["Protein<br/>Aggregation"]

Mutation["CHMP2B<br/>Mutations"]
LossFunction["Loss of<br/>Function"]

FTD["Frontotemporal<br/>Dementia"]
ALS["Amyotrophic<br/>Lateral Sclerosis"]
Dementia["Dementia<br/>Spectrum"]

Neuroinflam["Neuroinflammation"]
Neurodegeneration["Neurodegeneration"]
CellDeath["Neuronal<br/>Cell Death"]

Mutation -->|"causes"| CHMP2B
CHMP2B -->|"forms"| ESCRT
CHMP2B -->|"interacts"| CHMP2A
CHMP2B -->|"regulates"| VCP

ESCRT -->|"controls"| Endosome
ESCRT -->|"regulates"| Autophagy

LossFunction -->|"leads to"| Autophagy
Autophagy -->|"causes"| ProteinAgg
ProteinAgg -->|"triggers"| Neuroinflam

CHMP2B -->|"mutations activate"| FTD
CHMP2B -->|"associated with"| ALS
CHMP2B -->|"contributes to"| Dementia

Neuroinflam -->|"promotes"| Neurodegeneration
Neurodegeneration -->|"results in"| CellDeath

style CHMP2B fill:#006494
style ESCRT fill:#4a1a6b
style CHMP2A fill:#4a1a6b
style VCP fill:#4a1a6b
style Autophagy fill:#1b5e20
style Endosome fill:#1b5e20
style ProteinAgg fill:#ef5350
style Mutation fill:#ef5350
style LossFunction fill:#ef5350
style FTD fill:#

CHMP2B

Pathway Diagram

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CHMP2B</th>
</tr>
<tr> [@frontotemporal2018]
<td class="label">Gene</td> [@lessons2021]
<td>[CHMP2B](/genes/chmp2b)</td> [@enhanced2022]
</tr> [@uniprot]
<tr> [@page2026]
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q9UQN3" target="_blank">Q9UQN3</a></td>
</tr>
<tr>
<td class="label">PDB</td>
<td>N/A</td>
</tr>
<tr>
<td class="label">Mol. Weight</td>
<td>24 kDa</td>
</tr>
<tr>
<td class="label">Localization</td>
<td>[Endosomes and endolysosomal membranes](/mechanisms/lysosome-dysfunction)</td>
</tr>
<tr>
<td class="label">Family</td>
<td>[ESCRT-III complex](/entities/autophagy) family</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Frontotemporal Dementia](/diseases/ftd), <a href="/diseases/als">ALS<sup><a href="#references" class="ref-link" data-ref-number="5" data-ref-text="Frontotemporal Dementia causative CHMP2B impairs neuronal endolysosomal traffic-rescue by [TMEM106B](/proteins/tmem106b-protein) knockdown. Brain, 2018. DOI" data-ref-title="DOI" data-ref-authors="" data-ref-journal="" data-ref-year="2018" data-ref-url="https://doi.org/10.1093/brain/awy284" title="Frontotemporal Dementia causative CHMP2B impairs neuronal endolysosomal traffic-rescue by [TMEM106B](/proteins/tmem106b-protein) knockdown. Brain, 2018. DOI">5</a></sup></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a></td>
</tr>
<tr>
<td class="label">SciDEX Hypotheses</td>
<td><a href="/hypothesis/h-8986b8af" style="color:#ce93d8" title="Score: 0.43">Lysosomal Membrane Repair Enhancement...</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">188 edges</a></td>
</tr>
</table>

CHMP2B

Introduction

Chmp2B is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

CHMP2B is a protein encoded by the [CHMP2B](/proteins/chmp2b-protein) gene. It belongs to the [ESCRT-III complex](/entities/autophagy) family family and has a molecular weight of approximately 24 kDa[@mutations2005]. This protein is localized to [Endosomes and endolysosomal membranes](/mechanisms/lysosome-dysfunction) and plays a significant role in the pathogenesis of [Frontotemporal Dementia](/diseases/frontotemporal-dementia), [ALS](/diseases/als).

Structure

CHMP2B has been characterized structurally through X-ray crystallography and cryo-EM. Available PDB structures include: No structures deposited.

The protein's three-dimensional structure can also be explored via the [AlphaFold Protein Structure Database](https://alphafold.ebi.ac.uk/entry/Q9UQN3).

Normal Function

Under physiological conditions, CHMP2B performs essential functions in the nervous system. It is primarily found in [Endosomes and endolysosomal membranes](/mechanisms/lysosome-dysfunction) and contributes to normal cellular homeostasis, signaling, and neuronal function.

ESCRT Complex Function

CHMP2B is a member of the ESCRT-III (Endosomal Sorting Complex Required for Transport III) machinery, which plays critical roles in:

• Multivesicular body (MVB) formation: Sorting ubiquitinated cargo into intralumenal vesicles
• Endosomal trafficking: Regulating receptor degradation and recycling
• Lysosomal delivery: Directing cargo to lysosomes for degradation
• Autophagosome-lysosome fusion: Supporting [autophagy](/entities/autophagy) completion
• Cytokinesis: Facilitating membrane fission during cell division

Pathogenic Mutations

Several pathogenic mutations in CHMP2B have been linked to familial frontotemporal dementia (FTD) and ALS:

• p.Arg69His: First identified in Danish FTD families, causes endolysosomal trafficking defects
• p.Ile94Thr: Impairs ESCRT-III polymerization and function
• p.Gln206X: Truncation mutation leading to loss of function
• p.Asp187Val: Disrupts protein-protein interactions

• Accumulation of enlarged endosomes
• Impaired autophagic flux
• Reduced degradation of neurodegenerative disease proteins ([tau](/proteins/tau), [α-synuclein](/proteins/alpha-synuclein), TDP-43)
• Neuronal vulnerability and death

Therapeutic Implications

Given CHMP2B's central role in endolysosomal trafficking, therapeutic strategies include:

Interacting Proteins

CHMP2B interacts with several key proteins in its function:

• VPS4: AAA ATPase required for ESCRT-III disassembly
• CHMP2A: Paralog that compensates for CHMP2B function
• CHMP4B: Core ESCRT-III subunit
• TMEM106B: Lysosomal transmembrane protein modified by FTD-risk variants
• p62/SQSTM1: Autophagy receptor linking ubiquitinated cargo to autophagosomes
• OPTN: Optineurin, another FTD/ALS-associated autophagy receptor

Role in Disease

CHMP2B is implicated in the following neurodegenerative conditions:

• [Frontotemporal Dementia](/diseases/frontotemporal-dementia)
• [ALS](/diseases/als)

Therapeutic Targeting

CHMP2B represents an important therapeutic target. Multiple drug development programs are exploring strategies to modulate its function, reduce toxic forms, or enhance clearance mechanisms.

External Links

• UniProt: [https://www.uniprot.org/uniprot/Q9UQN3](https://www.uniprot.org/uniprot/Q9UQN3)
• AlphaFold: [CHMP2B](https://alphafold.ebi.ac.uk/entry/Q9UQN3)
• PDB: No structures deposited

See Also

• [Proteins Index](/proteins)
• [Genes Index](/genes)
• [Diseases Index](/diseases)
• [Mechanisms Index](/mechanisms)

Brain Atlas Resources

• Allen Human Brain Atlas: [CHMP2B expression search](https://human.brain-map.org/microarray/search/show?search_term=CHMP2B)
• Allen Mouse Brain Atlas: [CHMP2B search](https://mouse.brain-map.org/search/index.html?query=CHMP2B)
• Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
• BrainSpan Developmental Transcriptome: [CHMP2B developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=CHMP2B)

Background

The study of Chmp2B has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

Related Hypotheses

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

• [Lysosomal Membrane Repair Enhancement](/hypothesis/h-8986b8af) — <span style="color:#ffd54f;font-weight:600">0.43</span> · Target: CHMP2B

Pathway Diagram

The following diagram shows the key molecular relationships involving CHMP2B discovered through SciDEX knowledge graph analysis: