gene

CHMP2B

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about CHMP2B: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

441Connections

2Hypotheses

2Analyses

50Outgoing

50Incoming

2Experiments

2Debates

Summary

CHMP2B encodes a core ESCRT-III subunit. Mutations cause FTD-3 and ALS through impaired autophagy and endosomal trafficking dysfunction.

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🧬 Gene Info

Gene Symbol	CHMP2B
Full Name	Charged Multivesicular Body Protein 2B
Chromosome	3p11.2
Protein Family	ESCRT-III complex family
Protein Type	Other
Target Class	Other
Function	Under physiological conditions, CHMP2B performs essential functions in the nervous system.
Mechanism of Action	Therapeutic agents targeting CHMP2B would modulate ESCRT-III complex function to enhance endosomal sorting and autophagy, potentially clearing protein aggregates associated with frontotemporal dementia or compensating for loss-of-function mutations. Strategies include antisense oligonucleotides to modulate protein expression, autophagy enhancers to promote cellular clearance pathways, or small molecules that stabilize ESCRT-III complex assembly and function.
Primary Expression	Endosomes and endolysosomal membranes
Druggability	Low (0.32)
Clinical Stage	Phase II
Molecular Weight	24 kDa
Amino Acids	213 aa
Pathways	Lysosomal function / degradation
UniProt ID	Q9UQN3
GeneCards	CHMP2B
Human Protein Atlas	CHMP2B
Associated Diseases	Als, Alzheimer's disease, Amyotrophic Lateral Sclerosis, dementia
Known Drugs/Compounds	rapamycin
Interactions	Actin, ALS, ALS-CAUSING MUTATIONS, ALZHEIMER, App, ATG
SciDEX Target	View Target Profile (2 clinical trials)
SciDEX Hypotheses	Lysosomal Membrane Repair Enhancement
KG Connections	435 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🔮 Predicted Structure: CHMP2B — AlphaFold Q9UQN3 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (4)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

flowchart TD
    CHMP2B["CHMP2B
Charged Multivesicular
Body Protein 2B"]
    
    ESCRT["ESCRT-III
Complex"]
    CHMP2A["CHMP2A
Related Protein"]
    VCP["VCP/Valosin
Containing Protein"]
    
    Autophagy["Autophagy
Dysfunction"]
    Endosome["Endosomal
Trafficking"]
    ProteinAgg["Protein
Aggregation"]
    
    Mutation["CHMP2B
Mutations"]
    LossFunction["Loss of
Function"]
    
    FTD["Frontotemporal
Dementia"]
    ALS["Amyotrophic
Lateral Sclerosis"]
    Dementia["Dementia
Spectrum"]
    
    Neuroinflam["Neuroinflammation"]
    Neurodegeneration["Neurodegeneration"]
    CellDeath["Neuronal
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:#5d4400
    style ALS fill:#5d4400
    style Dementia fill:#5d4400
    style Neuroinflam fill:#ef5350
    style Neurodegeneration fill:#ef5350
    style CellDeath fill:#ef5350

Outgoing (314)

Target	Relation	Type	Str
Tau Aggregation Propagation	promotes	process	0.95
ESCRT pathway	involved_in	pathway	0.95
Nuclear Export Signal	interacts_with	mechanism	0.95
FTD3	associated_with	disease	0.95
Cortical Neurons	expressed_in	cell_type	0.90
Cell Nucleus	transports	cell_type	0.90
Frontotemporal Dementia	associated_with	disease	0.90
frontotemporal_dementia	causes	disease	0.90
C-terminus nuclear export signal	associated_with	process	0.90
nuclear export signal	mediates	process	0.90
cortical neurons	expressed_in	cell_type	0.85
Amyotrophic Lateral Sclerosis	associated_with	disease	0.85
Autophagy	associated_with	pathway	0.85
ESCRT-III	interacts_with	protein	0.85
autophagy	regulates	pathway	0.85
autophagy pathway	participates_in	pathway	0.80
Vesicle Trafficking	involved_in	process	0.80
CHMP2B_protein	encodes	protein	0.80
endosome	causes	organelle	0.70
endosome	transported_by	organelle	0.70
frontotemporal dementia	associated_with	disease	0.70
lysosomal_membrane_repair	regulates	mechanism	0.70
neurons	interacts_with	cell_type	0.70
oxidative stress response	participates_in	pathway	0.70
neurons	causes	cell_type	0.70
frontotemporal dementia	causes	disease	0.70
Ftd	activates	disease	0.65
Neurodegeneration	causes	disease	0.65
Amyotrophic Lateral Sclerosis	causes	disease	0.65
Dementia	causes	disease	0.65
Als	causes	disease	0.65
Frontotemporal Dementia	causes	disease	0.65
Dementia	associated_with	disease	0.65
Ms	associated_with	disease	0.65
Als	therapeutic_target	disease	0.65
Amyotrophic Lateral Sclerosis	activates	disease	0.65
ALS	activates	disease	0.65
Neurodegeneration	inhibits	disease	0.65
Frontotemporal Dementia	activates	disease	0.65
ALS	inhibits	disease	0.65
Alzheimer	stabilizes	disease	0.65
Als	stabilizes	disease	0.65
Ftd	associated_with	disease	0.65
Dementia	stabilizes	disease	0.65
Frontotemporal Dementia	stabilizes	disease	0.65
Dementia	activates	disease	0.65
Ms	activates	disease	0.65
neurodegeneration	associated_with	disease	0.65
Alzheimer	activates	disease	0.65
Ftd	causes	disease	0.65

Incoming (127)

Source	Relation	Type	Str
genes-chmp2b	linked_to	wiki	1.00
h-8986b8af	targets	hypothesis	0.90
SNCA	associated_with	protein	0.88
SNCA	interacts_with	protein	0.85
CRM1	mediates	protein	0.85
CHMP2A	interacts_with	gene	0.80
FIG4	causes	gene	0.60
SQSTM1	causes	gene	0.60
C9ORF72	causes	gene	0.60
GAIN	causes	gene	0.60
OPTN	causes	gene	0.60
ALS2	causes	gene	0.60
RAB5	causes	gene	0.60
UBIQUITIN	activates	gene	0.60
TDP-43	activates	gene	0.60
ATG7	inhibits	gene	0.60
ATG5	inhibits	gene	0.60
CHMP4B	activates	gene	0.60
OPTN	transports	gene	0.60
ALS2	transports	gene	0.60
VESICLE TRAFFICKING	causes	gene	0.60
AMYOTROPHIC LATERAL SCLEROSIS	causes	gene	0.60
ALS	interacts_with	gene	0.60
ANXA11	causes	gene	0.60
CCNF	causes	gene	0.60
CHCHD10	causes	gene	0.60
CHCHD2	causes	gene	0.60
ANXA11	associated_with	gene	0.60
CCNF	associated_with	gene	0.60
CHCHD10	associated_with	gene	0.60
CHCHD2	associated_with	gene	0.60
C9ORF72 REPEAT EXPANSION	activates	gene	0.60
LYSOSOMAL BIOGENESIS	causes	gene	0.60
DEMENTIA	causes	gene	0.60
NEURODEGENERATION	causes	gene	0.60
ENDOSOMES	causes	gene	0.60
ALZHEIMER	stabilizes	gene	0.60
DEMENTIA	stabilizes	gene	0.60
ALS	transports	gene	0.60
NEURODEGENERATION	activates	gene	0.60
DEMENTIA	associated_with	gene	0.60
RAB5	expressed_in	gene	0.60
SQSTM1	associated_with	gene	0.60
GAIN	expressed_in	gene	0.60
CHMP2A	activates	gene	0.60
C9ORF72	activates	gene	0.60
VALOSIN	activates	gene	0.60
TAU	activates	gene	0.60
GENES	associated_with	gene	0.60
ALZHEIMER	activates	gene	0.60

Targeting Hypotheses (2)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Lysosomal Membrane Repair Enhancement	0.538	neurodegeneration	Autophagy-lysosome pathway convergence a
CHMP2B vs. CHMP2A Subunit Targeting Creates a Therapeutic Wi	0.330	neurodegeneration	What is the therapeutic window between t

Mentioning Analyses (2)

Scientific analyses that reference this entity

Autophagy-lysosome pathway convergence across neurodegenerative diseases

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.921

Autophagy-lysosome pathway convergence across neurodegenerative diseases

neurodegeneration | 2026-04-01 | 0 hypotheses

Experiments (2)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Autophagy Enhancement Drug Screening for Neurodegeneration	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$6,550,000
Presymptomatic GRN Carrier Intervention Timing — Biomarker-Guided Ther	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Autophagy and ALS: mechanistic insights and therapeutic implications. [PMID:34057020]	Chua JP, De Calbiac H, Kabashi E, Barmad	Autophagy	2022	2
α-Synuclein aggregates inhibit ESCRT-III through sequestration and collateral de [PMID:40934925]	Sitron CS, Trinkaus VA, Galesic A, Garha	Mol Cell	2025	1
Compromised function of the ESCRT pathway promotes endolysosomal escape of tau s [PMID:31578281]	Chen JJ, Nathaniel DL, Raghavan P, Nelso	J Biol Chem	2019	1
Mislocalization of FTD3-associated mutant CHMP2B to the nucleus of human neurons [PMID:41559796]	["Jun Y", "Hass E", "Lee S", "Fazzio T",	Acta neuropathologica communic	2026	0
Spatially resolved translational dysregulation in [PMID:41509319]	["Wu M", "Huang J", "Aryal S", "Farsi Z"	bioRxiv : the preprint server	2025	0
Increased granulovacuolar degeneration in the thalamus and higher neurofibrillar [PMID:40889877]	["Nagakura A", "Kawakami I", "Kimura A",	Psychiatry and clinical neuros	2025	0
Loss of CHMP2A implicates an ordered assembly of ESCRT-III proteins during cytok [PMID:40928930]	Kamenetsky N, Nachmias D, Khan S, Avinoa	Molecular biology of the cell	2025	0
The multi-dimensional regulatory mechanism of Sirt6 in heart health: From cell d [PMID:40902544]	Zhan S, Guo C, Yan H, Zheng G, Yan D	Biochemical and biophysical re	2025	0
Targeted autophagic clearance of Tau protects against Alzheimer's disease throug [PMID:40963907]	Yoon BH, Kim J, Sengupta S, Park CJ, Ko	Theranostics	2025	0
Pathological α-synuclein elicits granulovacuolar degeneration independent of tau [PMID:40537859]	["Dues D", "Erb M", "Kasen A", "Vatsa N"	Translational neurodegeneratio	2025	0
Classical swine fever virus recruits ALIX and ESCRT-III to facilitate viral budd [PMID:39998268]	["Chen J", "Yang H", "Wan M", "Cheng Y",	mBio	2025	0
The Ku80-p53-SIRT1 axis in DNA damage response contributes to sporadic and famil [PMID:41422089]	["Jun Y", "Lee S", "Almeida S", "Freude	Nature communications	2025	0
Truncation mutation of CHMP2B disrupts late endosome function but reduces TDP-43 [PMID:40316175]	["Iguchi Y", "Takahashi Y", "Li J", "Ama	Neurochemistry international	2025	0
The expanding repertoire of ESCRT functions in cell biology and disease. [PMID:40562928]	Hurley JH, Coyne AN, Miączyńska M, Stenm	Nature	2025	0
Methylation of ESCRT-III components regulates the timing of cytokinetic abscissi [PMID:38740816]	Richard A, Berthelet J, Judith D, Advedi	Nature communications	2024	0
Extracellular NCOA4 is a mediator of septic death by activating the AGER-NFKB pa [PMID:38916095]	["Liu J", "Wang Y", "Zeng L", "Yu C", "K	Autophagy	2024	0
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorder [PMID:34130600]	Deneubourg C, Ramm M, Smith LJ, Baron O,	Autophagy	2022	0
Lessons learned from CHMP2B, implications for frontotemporal dementia and amyotr [PMID:33144171]	Ugbode C, West RJH	Neurobiology of disease	2021	0
Expression of mutant CHMP2B linked to neurodegeneration in humans disrupts circa [PMID:32123847]	["Lee D", "Zheng X", "Shigemori K", "Kra	FASEB bioAdvances	2019	0
Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced m [PMID:29400714]	Shi Y, Lin S, Staats KA, Li Y, Chang WH,	Nature medicine	2018	0

Debates (2)

Multi-agent debates referencing this entity

Multiple NDDs converge on autophagy-lysosome dysfunction. Are there universal th

closed · Rounds: 4 · Score: 0.90 · 2026-04-06

What are the mechanisms underlying autophagy-lysosome pathway convergence across

closed · Rounds: 5 · Score: 0.95 · 2026-04-01

Related Research

Hypotheses and analyses mentioning CHMP2B in their description or question text

No additional research found

CHMP2B

Understanding Entity Pages

Summary

Wiki Pages (4)

CHMP2B — Charged Multivesicular Body Protein 2B

CHMP2B Protein

CHMP2B and ESCRT-III Dysfunction in Frontotemporal Dementia

CHMP2B

Pathway Diagram

Outgoing (314)

Incoming (127)

Targeting Hypotheses (2)

Mentioning Analyses (2)

Autophagy-lysosome pathway convergence across neurodegenerative diseases

Autophagy-lysosome pathway convergence across neurodegenerative diseases

Experiments (2)

Related Papers (20)

Debates (2)

Multiple NDDs converge on autophagy-lysosome dysfunction. Are there universal th

What are the mechanisms underlying autophagy-lysosome pathway convergence across

Related Research