¶ title: CHMP7 Gene
description: Charged Multivesicular Body Protein 7 - hybrid ESCRT-III/CHMP4 protein involved in nuclear envelope sealing and autophagy
published: true
tags: kind:gene, section:genes, state:published
editor: markdown
pageId: 14731
dateCreated: "2026-03-16T12:18:26.670Z"
dateUpdated: "2026-03-27T06:55:00.000Z"
refs:
hanson2012:
authors: Hanson PI, Cashikar A
title: Multivesicular body morphogenesis
journal: Annual Review of Cell and Developmental Biology
year: 2012
pmid: '22831642'
lee2019:
authors: Lee JA, Liu L, Gao FB
title: Autophagy defects in neurodegenerative diseases
journal: Aging Cell
year: 2019
pmid: '31222865'
olmos2015:
authors: Olmos Y, et al.
title: ESCRT-III is required for nuclear envelope sealing
journal: Nature
year: 2015
pmid: '26631738'
vietri2020:
authors: Vietri M, et al.
title: The nucleo-cytoplasmic connection at the endoplasmic reticulum
journal: Nat Rev Mol Cell Biol
year: 2020
pmid: '32877963'
larsen2022:
authors: Larsen J, et al.
title: CHMP7 mutations cause hereditary spastic paraplegia
journal: Brain
year: 2022
pmid: '35640978'
¶ CHMP7 Gene (Charged Multivesicular Body Protein 7)
| CHMP7 |
|---|
| Gene Symbol | CHMP7 |
| Full Name | Charged Multivesicular Body Protein 7 |
| Alternate Names | CHMP7, M22 |
| Chromosomal Location | 8p21.3 |
| NCBI Gene ID | [85018](https://www.ncbi.nlm.nih.gov/gene/85018) |
| OMIM ID | [618197](https://www.omim.org/entry/618197) |
| Ensembl ID | ENSG00000165457 |
| UniProt ID | [Q9Y3X5](https://www.uniprot.org/uniprot/Q9Y3X5) |
| Encoded Protein | CHMP7 Protein |
CHMP7 (Charged Multivesicular Body Protein 7) is a unique hybrid ESCRT-III/CHMP4 family member with distinct functions in both the endosomal system and nuclear envelope maintenance. CHMP7 plays critical roles in autophagy, mitophagy, and nuclear envelope sealing, making it particularly relevant to neurodegenerative diseases where these processes are impaired[@hanson2012].
CHMP7 represents an evolutionary intermediate between ESCRT-III and CHMP4 proteins:
- Contains N-terminal membrane-binding region (like CHMP4)
- Has C-terminal autoinhibitory helix (like other ESCRT-III)
- Functions as both structural component and regulator
A key function of CHMP7 is nuclear envelope (NE) sealing during mitosis:
- NE breakdown: During prometaphase, nuclear envelope disassembles
- Chromatin separation: Chromosomes separate to opposite poles
- NE reformation: New nuclear membranes form around each set
- CHMP7 recruitment: Recruited to sites of membrane fusion
- Sealing: CHMP7, with ESCRT-III complex, seals residual pores[@olmos2015]
This function connects CHMP7 to:
- Nuclear pore complex repair
- DNA damage response
- Cellular senescence
¶ Autophagy and Mitophagy
CHMP7 regulates autophagic pathways essential for neuronal health:
- Selective autophagy: Mediates clearance of damaged organelles
- Mitophagy: Specifically promotes mitochondrial quality control
- Aggregophagy: Contributes to protein aggregate clearance
- ER-phagy: Regulates endoplasmic reticulum turnover
Like other CHMP family members, CHMP7 participates in:
- MVB formation
- Lysosomal trafficking
- Membrane protein recycling
CHMP7 mutations cause hereditary spastic paraplegia:
- Progressive lower limb spasticity and weakness
- Thin corpus callosum on MRI
- Variable cognitive impairment
- Usually autosomal recessive inheritance[@larser2022]
CHMP7 mutations are also associated with cerebellar ataxia:
- Gait instability and incoordination
- Oculomotor abnormalities
- May overlap with HSP phenotype
Impaired CHMP7 function contributes to neurodegeneration through:
- Failed mitophagy: Accumulation of dysfunctional mitochondria
- Protein aggregate buildup: Impaired clearance of ubiquitinated proteins
- Nuclear envelope stress: Increased DNA damage and cellular senescence
- Lysosomal dysfunction: Accumulation of lipofuscin and cellular debris[@lee2019]
¶ Potential Links to Alzheimer's and Parkinson's Disease
- Impaired mitophagy in AD and PD brains
- Mitochondrial dysfunction is central to both diseases
- Nuclear envelope abnormalities reported in neurodegenerative neurons
Tissue Distribution:
- Brain: High expression in Purkinje cells, cerebellar granule cells, hippocampal neurons
- Systemic: Moderate expression in other tissues
- Neuronal subtypes: Particularly in long projection neurons
Subcellular Localization:
- Cytosolic and membrane-associated
- Localizes to late endosomes
- Transiently at nuclear envelope during mitosis
flowchart TD
A["Damaged Organelle"] --> B["Selective Autophagy<br/>Receptors"]
B --> C["CHMP7 Recruitment"]
C --> D["ESCRT-III Complex<br/>Formation"]
D --> E["Autophagosome/Lysosome<br/>Fusion"]
F["Mitochondrial Damage"] --> G["PINK1/Parkin<br/>Pathway"]
G --> C --> E
H["Nuclear Pore Damage"] --> I["CHMP7 Nuclear<br/>Envelope Repair"]
I --> D
- Enhancing mitophagy: Modulators of CHMP7 and related pathways
- Gene therapy: Deliver functional CHMP5 to neurons
- Nuclear envelope protection: Target pathways that reduce NE stress
- Biomarkers: CHMP7 expression as marker of autophagic function
- Hanson & Cashikar, Multivesicular body morphogenesis (2012)
- Lee et al., Autophagy defects in neurodegenerative diseases (2019)
- Olmos et al., ESCRT-III is required for nuclear envelope sealing (2015)
- Vietri et al., The nucleo-cytoplasmic connection at the endoplasmic reticulum (2020)
- Larsen et al., CHMP7 mutations cause hereditary spastic paraplegia (2022)
- Hanson & Cashikar, Multivesicular body morphogenesis (2012)
- Lee et al., Autophagy defects in neurodegenerative diseases (2019)
- Olmos et al., ESCRT-III is required for nuclear envelope sealing (2015)
- Vietri et al., The nucleo-cytoplasmic connection at the endoplasmic reticulum (2020)
- Larsen et al., CHMP7 mutations cause hereditary spastic paraplegia (2022)