CHMP7 mutations cause hereditary spastic paraplegia

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gene797 wordssynced 2026-04-02

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

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

Mermaid diagram (expand to render)

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:

Mermaid diagram (expand to render)

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