CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10

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CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10

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CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10</th>
</tr>
<tr> [@zhou2023]
<td class="label">Symbol</td> [@zhou2024]
<td><strong>CHCHD10</strong></td> [@straub2021]
</tr> [@anderson2019]
<tr> [@gao2025]
<td class="label">Full Name</td>
<td>Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>22q11.23</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/400916" target="_blank">400916</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000250479" target="_blank">ENSG00000250479</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/615903" target="_blank">615903</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q8WYQ3" target="_blank">Q8WYQ3</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[ALS](/diseases/als), [FTD](/diseases/ftd), Mitochondrial Myopathy</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Motor cortex, Spinal cord, Mitochondria (widespread)</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Mutations</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">S59L<br>R15L<br>G66V<br>G58R<br>P34S</td>
</tr>

...

CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10</th>
</tr>
<tr> [@zhou2023]
<td class="label">Symbol</td> [@zhou2024]
<td><strong>CHCHD10</strong></td> [@straub2021]
</tr> [@anderson2019]
<tr> [@gao2025]
<td class="label">Full Name</td>
<td>Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>22q11.23</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/400916" target="_blank">400916</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000250479" target="_blank">ENSG00000250479</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/615903" target="_blank">615903</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q8WYQ3" target="_blank">Q8WYQ3</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[ALS](/diseases/als), [FTD](/diseases/ftd), Mitochondrial Myopathy</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Motor cortex, Spinal cord, Mitochondria (widespread)</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Mutations</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">S59L<br>R15L<br>G66V<br>G58R<br>P34S</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><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/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">22 edges</a></td>
</tr>
</table>

CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10

Introduction

Chchd10 — Coiled Coil Helix Coiled Coil Helix Domain Containing 10 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

Mermaid diagram (expand to render)

CHCHD10 (Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10) is a nuclear-encoded mitochondrial gene located on chromosome 22q11.23 that was identified as a cause of familial ALS-FTD in 2014 ([Bannwarth et al., 2014](https://doi.org/10.1093/brain/awu138)). The gene encodes a small protein (~14 kDa) localized to the mitochondrial intermembrane space (IMS), where it plays a role in maintaining cristae morphology and oxidative phosphorylation (OXPHOS) complex integrity. Mutations in CHCHD10 produce a broad clinical spectrum encompassing motor neuron disease, frontotemporal dementia, mitochondrial myopathy, cardiomyopathy, and cerebellar ataxia ([Ajroud-Driss et al., 2015](https://doi.org/10.1001/jamaneurol.2014.4197)). The gene is catalogued as NCBI Gene ID [400916](https://www.ncbi.nlm.nih.gov/gene/400916) and OMIM [615903](https://omim.org/entry/615903).

Function

Mitochondrial Cristae Maintenance

CHCHD10 resides in the mitochondrial intermembrane space at cristae junctions, where it forms a complex with its paralog CHCHD2. Together they stabilize the mitochondrial contact site and cristae organizing system (MICOS), which maintains cristae morphology essential for efficient OXPHOS ([Genin et al., 2016](https://doi.org/10.1007/s00401-015-1516-y)). Loss of CHCHD10 function leads to cristae disorganization, impaired respiratory chain activity, and reduced ATP production.

Oxidative Phosphorylation

CHCHD10 is required for the stability of OXPHOS complexes, particularly complexes I and IV. Mutant CHCHD10 causes defective mitochondrial respiration, leading to energy deficits that are particularly damaging to metabolically demanding motor neurons ([Woo et al., 2017](https://doi.org/10.1038/ncomms15558)).

CHCHD10 and CHCHD2 Relationship

CHCHD10 and its paralog CHCHD2 form heterodimers through their CHCH domains. While CHCHD10 mutations are primarily associated with ALS-FTD, CHCHD2 mutations cause familial Parkinson's disease, suggesting overlapping but distinct roles in neurodegeneration ([Zhou et al., 2023](https://doi.org/10.1007/s12264-022-01007-y)).

Brain Expression

CHCHD10 is expressed in mitochondria throughout the body, with particularly high expression in metabolically active tissues including the motor cortex, spinal cord, skeletal muscle, and heart. Expression data is available from the [Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=CHCHD10).

Disease Associations

CHCHD10 mutations produce a remarkably broad phenotypic spectrum:

Amyotrophic Lateral Sclerosis (ALS) — Motor neuron degeneration with upper and lower motor neuron signs.
Frontotemporal Dementia (FTD) — Behavioral variant FTD or progressive aphasia.
Mitochondrial myopathy — Proximal muscle weakness, ragged red fibers, COX-negative fibers.
Cardiomyopathy — Cardiac involvement in some families with S59L.
Spinal Muscular Atrophy Jokela type — Caused by p.G66V, presenting as late-onset proximal SMA.
Cerebellar ataxia — Some mutations produce cerebellar signs.

Key Mutations

| Mutation | Disease Phenotype | Mechanism |
|----------|------------------|-----------|
| S59L | ALS-FTD, myopathy, cardiomyopathy | Gain-of-function through toxic amyloid fibril formation ([Zhou et al., 2024](https://doi.org/10.1038/s41467-025-62149-3)); disrupts cristae and triggers mitochondrial integrated stress response |
| R15L | ALS-FTD | Milder phenotype; located in the disordered N-terminal domain |
| G66V | Spinal Muscular Atrophy Jokela type | Disrupts CHCH domain folding |
| G58R | Isolated mitochondrial myopathy | Autosomal dominant, restricted to muscle |
| P34S | ALS-FTD (variable penetrance) | Located in disordered region; pathogenicity debated |

Pathogenic Mechanisms

Toxic amyloid aggregation (gain of function): The disordered N-terminal domain of CHCHD10 forms amyloid fibrils, and disease-associated mutations (particularly S59L) promote different protofilament folds. CryoEM structures reveal that S59L cannot be accommodated within wild-type fibril conformations, driving toxic gain-of-function aggregation ([Zhou et al., 2024](https://doi.org/10.1038/s41467-025-62149-3)).

Mitochondrial dysfunction: Mutant CHCHD10 disrupts cristae architecture and OXPHOS, causing energy failure.

Mitochondrial integrated stress response: S59L triggers metabolic rewiring and activation of both ER and mitochondrial unfolded protein responses ([Straub et al., 2021](https://doi.org/10.1093/hmg/ddab078)).

TDP-43 mislocalization: Loss of CHCHD10 function causes cytoplasmic accumulation of TDP-43, linking mitochondrial dysfunction to a hallmark of ALS-FTD pathology ([Woo et al., 2017](https://doi.org/10.1038/ncomms15558)).

Mitochondrial fragmentation: In C. elegans models, CHCHD10 orthologue mutations cause progressive motor neuron degeneration and mitochondrial fragmentation ([Gao et al., 2025](https://doi.org/10.1093/hmg/ddaf064)).

Therapeutic Implications

Mitochondrial protective agents: Compounds that stabilize cristae morphology or boost OXPHOS.
Anti-aggregation strategies: Targeting the amyloidogenic N-terminal domain of CHCHD10.
Mitochondrial stress response modulators: Modulating the integrated stress response to prevent maladaptive outcomes.

External Links

NCBI Gene: [https://www.ncbi.nlm.nih.gov/gene/400916](https://www.ncbi.nlm.nih.gov/gene/400916)
Ensembl: [https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000250479](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000250479)
OMIM: [https://omim.org/entry/615903](https://omim.org/entry/615903)
UniProt: [https://www.uniprot.org/uniprot/Q8WYQ3](https://www.uniprot.org/uniprot/Q8WYQ3)
Allen Human Brain Atlas: [CHCHD10 expression](https://human.brain-map.org/microarray/search/show?search_term=CHCHD10)
[Genes Index](/genes/genes)
[SOD1 — Superoxide Dismutase 1](/genes/ide)
[FUS — Fused in Sarcoma](/genes/ar)
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
[Frontotemporal Dementia](/diseases/frontotemporal-dementia)
[Mitochondrial Dysfunction and Oxidative Stress in AD](/genes/dysf)
[--](/proteins/n--cadherin-protein)

Background

The study of Chchd10 — Coiled Coil Helix Coiled Coil Helix Domain Containing 10 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.

Brain Atlas Resources

[Allen Human Brain Atlas search: CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10](https://human.brain-map.org/search?searchText=CHCHD10)
[Allen Mouse Brain Atlas search: CHCHD10](https://mouse.brain-map.org/search/index.html?query=CHCHD10)
[Allen Brain Map portal search: CHCHD10](https://portal.brain-map.org/search?query=CHCHD10)
[BrainSpan developmental transcriptome search: CHCHD10](https://www.brainspan.org/search/index.html?search=CHCHD10)

Allen Brain Atlas Resources

CHCHD10 expression data available from the Allen Brain Atlas:

[Human Brain Atlas - CHCHD10 Expression](https://human.brain-map.org/microarray/search/show?search_term=CHCHD10): Gene expression data across brain regions
[Allen Cell Type Atlas](https://celltypes.brain-map.org/): Cellular expression patterns in specific neuronal types
[BrainSpan Atlas of the Developing Human Brain](https://brainspan.org/): Developmental expression patterns

Recent Publications (2024-2026)

Recent research on CHCHD10 has expanded our understanding of its role in ALS/FTD:

[Petel Légaré et al., CHCHD10(P80L) knock-in zebrafish display mild ALS-like phenotype (2024)](https://pubmed.ncbi.nlm.nih.gov/39260590/) — Zebrafish model shows mild ALS-like phenotype.

[Maitra et al., FDA-approved PDE4 inhibitors reduce CHCHD10 toxicity (2024)](https://pubmed.ncbi.nlm.nih.gov/38895204/) — PDE4 inhibitors reduce toxicity of ALS-FTD-associated CHCHD10 (S59L).

[Southwell et al., High fat diet ameliorates CHCHD10 mutant cardiomyopathy (2024)](https://pubmed.ncbi.nlm.nih.gov/38724625/) — High fat diet ameliorates mitochondrial cardiomyopathy in CHCHD10 mutant mice.

[Genin et al., CHCHD10(S59L/+) mouse model features of FTD (2024)](https://pubmed.ncbi.nlm.nih.gov/38583639/) — Behavioral and neuropathological features of frontotemporal dementia in CHCHD10 mouse model.

[Ikeda et al., CHCHD2 P14L exhibits cytoplasmic mislocalization (2024)](https://pubmed.ncbi.nlm.nih.gov/39131911/) — CHCHD2 P14L found in ALS exhibits cytoplasmic mislocalization and alters Ca2+ homeostasis.

References

[Bannwarth S, et al, A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement (2014)](https://doi.org/10.1093/brain/awu138)

[Ajroud-Driss S, et al, Mutation in the FUS/TLS gene on chromosome 16 causes familial amyotrophic lateral sclerosis (2015)](https://doi.org/10.1001/jamaneurol.2014.4197)

[Genin EC, et al, CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis (2016)](https://doi.org/10.1007/s00401-015-1516-y)

[Woo JA, et al, Loss of function CHCHD10 mutations in cytoplasmic TDP-43 accumulation and synaptic integrity (2017)](https://doi.org/10.1038/ncomms15558)

[Zhou ZD, et al, CHCHD2 and CHCHD10-related neurodegeneration: molecular pathogenesis and the path to precision therapy (2023)](https://doi.org/10.1007/s12264-022-01007-y)

[Zhou Q, et al, Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration (2024)](https://doi.org/10.1038/s41467-025-62149-3)

[Straub IR, et al, Multi-OMICS study of a CHCHD10 variant causing ALS demonstrates metabolic rewiring (2021)](https://doi.org/10.1093/hmg/ddab078)

[Anderson CJ, et al, ALS/FTD mutant CHCHD10 mice reveal a tissue-specific toxic gain-of-function and mitochondrial stress response (2019)](https://doi.org/10.1007/s00401-019-01989-y)

[Gao R, et al, har-1/CHCHD10 mutations induce neurodegeneration and mitochondrial fragmentation in *C (2025)](https://doi.org/10.1093/hmg/ddaf064)

Pathway Diagram

The following diagram shows the key molecular relationships involving CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

CHCHD10

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-chchd10
kg_node_id	CHCHD10
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-975baeeb34bd
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-chchd10'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

95%

Debates

0

Incoming

19

Outgoing

28

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10

CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10

CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10

CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10

Introduction

Overview

Function

Mitochondrial Cristae Maintenance

Oxidative Phosphorylation

CHCHD10 and CHCHD2 Relationship

Brain Expression

Disease Associations

Key Mutations

Pathogenic Mechanisms

Therapeutic Implications

External Links

Background

Brain Atlas Resources

Allen Brain Atlas Resources

Recent Publications (2024-2026)

References

Pathway Diagram

💬 Discussion