CHMP7 mutations cause hereditary spastic paraplegia

CHMP7 mutations cause hereditary spastic paraplegia

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 mutations cause hereditary spastic paraplegia

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)

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">CHMP7</th></tr>
<tr><td><b>Gene Symbol</b></td><td>CHMP7</td></tr>
<tr><td><b>Full Name</b></td><td>Charged Multivesicular Body Protein 7</td></tr>
<tr><td><b>Alternate Names</b></td><td>CHMP7, M22</td></tr>
<tr><td><b>Chromosomal Location</b></td><td>8p21.3</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>[85018](https://www.ncbi.nlm.nih.gov/gene/85018)</td></tr>
<tr><td><b>OMIM ID</b></td><td>[618197](https://www.omim.org/entry/618197)</td></tr>
<tr><td><b>Ensembl ID</b></td><td>ENSG00000165457</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q9Y3X5](https://www.uniprot.org/uniprot/Q9Y3X5)</td></tr>
<tr><td><b>Encoded Protein</b></td><td>CHMP7 Protein</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/infection" style="color:#ef9a9a">Infection</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">40 edges</a></td>
</tr>
</table>
</div>

Overview

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](/mechanisms/autophagy), [mitophagy](/mechanisms/mitophagy), and nuclear envelope sealing, making it particularly relevant to [neurodegenerative diseases](/diseases) where these processes are impaired[@hanson2012].

Function

Hybrid ESCRT-III/CHMP4 Structure

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

Nuclear Envelope Sealing

A key function of CHMP7 is nuclear envelope (NE) sealing during [mitosis](/mechanisms/cell-cycle-dysfunction):

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](/mechanisms/autophagy) 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

Late Endosomal Sorting

Like other CHMP family members, CHMP7 participates in:

• MVB formation
• Lysosomal trafficking
• Membrane protein recycling

Disease Associations

Hereditary Spastic Paraplegia (HSP)

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]

Cerebellar Ataxia

CHMP7 mutations are also associated with cerebellar ataxia:

• Gait instability and incoordination
• Oculomotor abnormalities
• May overlap with HSP phenotype

Neurodegeneration

Impaired CHMP7 function contributes to [neurodegeneration](/mechanisms/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

Expression

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

Pathway Interactions

Therapeutic Implications

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

Key Publications

[Hanson & Cashikar, Multivesicular body morphogenesis (2012)](https://pubmed.ncbi.nlm.nih.gov/22831642/)

[Lee et al., Autophagy defects in neurodegenerative diseases (2019)](https://pubmed.ncbi.nlm.nih.gov/31222865/)

[Olmos et al., ESCRT-III is required for nuclear envelope sealing (2015)](https://pubmed.ncbi.nlm.nih.gov/26631738/)

[Vietri et al., The nucleo-cytoplasmic connection at the endoplasmic reticulum (2020)](https://pubmed.ncbi.nlm.nih.gov/32877963/)

[Larsen et al., CHMP7 mutations cause hereditary spastic paraplegia (2022)](https://pubmed.ncbi.nlm.nih.gov/35640978/)

Cross-references

• [CHMP7 Protein](/proteins/chmp7-protein)
• [ESCRT Pathway](/mechanisms/esCRT-pathway)
• [Autophagy](/mechanisms/autophagy)
• [Mitophagy](/mechanisms/mitophagy)
• [Hereditary Spastic Paraplegia](/diseases/hereditary-spastic-paraplegia)
• [Cerebellar Ataxia](/diseases/cerebellar-ataxia)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

References

[Hanson & Cashikar, Multivesicular body morphogenesis (2012)](https://pubmed.ncbi.nlm.nih.gov/22831642/)

[Lee et al., Autophagy defects in neurodegenerative diseases (2019)](https://pubmed.ncbi.nlm.nih.gov/31222865/)

[Olmos et al., ESCRT-III is required for nuclear envelope sealing (2015)](https://pubmed.ncbi.nlm.nih.gov/26631738/)

[Vietri et al., The nucleo-cytoplasmic connection at the endoplasmic reticulum (2020)](https://pubmed.ncbi.nlm.nih.gov/32877963/)

[Larsen et al., CHMP7 mutations cause hereditary spastic paraplegia (2022)](https://pubmed.ncbi.nlm.nih.gov/35640978/)

Pathway Diagram

The following diagram shows the key molecular relationships involving CHMP7 mutations cause hereditary spastic paraplegia discovered through SciDEX knowledge graph analysis: