CHCHD10 Gene
Overview
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CHCHD10 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CHCHD10</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>22q11.23</td>
</tr>
<tr>
<td class="label">Gene Length</td>
<td>~4.2 kb</td>
</tr>
<tr>
<td class="label">Exons</td>
<td>3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>400916</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000250479</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>Q8WYQ3</td>
</tr>
<tr>
<td class="label">Mutation</td>
<td>Type</td>
</tr>
<tr>
<td class="label">S59L</td>
<td>Missense</td>
</tr>
<tr>
<td class="label">R15L</td>
<td>Missense</td>
</tr>
<tr>
<td class="label">G66V</td>
<td>Missense</td>
</tr>
<tr>
<td class="label">P34S</td>
<td>Missense</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 Gene plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Introduction
Chchd10 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. [@johnson2014]
CHCHD10 (Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10) is a gene located on chromosome 22q11.23 that encodes a mitochondrial protein essential for mitochondrial DNA maintenance, cristae organization, and neuronal survival [1](https://doi.org/10.1093/brain/awu224). Mutations in CHCHD10 are associated with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), mitochondrial myopathy, and a novel syndrome combining ALS with sensory ataxia [2](https://doi.org/10.1016/j.neurobiolaging.2014.05.005). [@strahm2015]
Gene Overview
Protein Structure
The CHCHD10 protein is a small mitochondrial protein (182 amino acids) characterized by:
- Twin CX9C motif: Two CX9C clusters that coordinate iron-sulfur (Fe-S) cluster binding, essential for mitochondrial Fe-S cluster assembly [3](https://doi.org/10.1093/brain/aww016)
- Coiled-coil domains: Facilitate protein-protein interactions and mitochondrial membrane association
- N-terminal targeting sequence: Directs import into the mitochondrial matrix
Molecular Function
Mitochondrial Genome Maintenance
CHCHD10 plays a critical role in stabilizing mitochondrial DNA (mtDNA) nucleoids and maintaining mtDNA copy number. It interacts with mitochondrial transcription factor A (TFAM) to facilitate mtDNA packaging and replication [4](https://doi.org/10.1093/hmg/ddv259).
Iron-Sulfur Cluster Assembly
As a Fe-S cluster binding protein, CHCHD10 participates in the mitochondrial Fe-S cluster assembly (ISCU) pathway, which is essential for the maturation of iron-sulfur proteins involved in oxidative phosphorylation (Complex I, II, III) [5](https://doi.org/10.1093/brain/awv295).
Oxidative Phosphorylation Complex Assembly
CHCHD10 directly interacts with key components of the electron transport chain:
- Complex I (NADH dehydrogenase): Assembly and stability
- Complex IV (Cytochrome c oxidase): Cristae organization and function
Expression Pattern
CHCHD10 shows high expression in:
- Motor [neurons](/entities/neurons): Spinal cord anterior horn cells, cortical motor neurons
- Cardiac muscle: High metabolic demand tissues
- Skeletal muscle: Type I (slow-twitch) fibers
- Brain regions: Motor [cortex](/brain-regions/cortex), basal ganglia, [hippocampus](/brain-regions/hippocampus)
Disease Associations
Amyotrophic Lateral Sclerosis (ALS15)
CHCHD10 mutations cause a distinct form of autosomal dominant ALS (ALS15) characterized by:
- Early onset: Typically 40-60 years of age
- Rapid progression: Median survival 2-3 years
- UMN and LMN involvement: Combined upper and lower motor neuron signs
- Cognitive involvement: Some patients develop FTD
The most common pathogenic variants include:
Frontotemporal Dementia (FTD)
CHCHD10 mutations can cause FTD with or without ALS, particularly affecting:
- Behavioral variant FTD (bvFTD): Personality changes, disinhibition
- Semantic variant: Language impairment
- ALS-FTD overlap syndrome
Mitochondrial Myopathy
Homozygous or compound heterozygous CHCHD10 mutations cause mitochondrial myopathy with:
- Progressive muscle weakness
- Ragged-red fibers on muscle biopsy
- Exercise intolerance
- Elevated CK levels
Sensory Ataxia Syndrome
A novel phenotype combining:
- Sensory loss and ataxia
- Motor neuronopathy
- Peripheral neuropathy
Pathogenic Mechanisms
Mitochondrial Dysfunction
CHCHD10 mutations lead to:
mtDNA depletion: Reduced mtDNA copy number in affected tissues
Complex I deficiency: Impaired NADH dehydrogenase activity
Cristae abnormalities: Disorganized mitochondrial cristae structure
Increased [reactive oxygen species](/entities/reactive-oxygen-species) (ROS): Oxidative stressIron-Sulfur Cluster Defects
Impaired Fe-S cluster assembly causes:
- Global Fe-S enzyme deficiency
- Iron accumulation in mitochondria
- Dysregulated iron homeostasis
Neuronal Vulnerability
Motor neurons are particularly vulnerable due to:
- High metabolic demands
- Long axons requiring efficient mitochondrial transport
- Limited antioxidant capacity
Therapeutic Implications
Mitochondrial-Targeted Therapies
- CoQ10 and analogs: Support mitochondrial electron transport
- Mitochondrial antioxidants: MitoQ, edaravone
- Fe-S cluster modulators: Iron chelation therapy
Gene Therapy Approaches
- AAV-CHCHD10: Viral delivery of wild-type CHCHD10
- CRISPR-based gene editing: Correct pathogenic mutations
- Antisense oligonucleotides: Reduce toxic mutant protein expression
Small Molecule Screening
- Mitochondrial biogenesis promoters: PGC-1α activators
- Fe-S cluster assembly pathway modulators
- [Autophagy](/entities/autophagy) enhancers: Promote mitophagy
Animal Models
- CHCHD10 knockout mice: Show mtDNA depletion and cardiomyopathy
- CHCHD10 S59L knock-in mice: Recapitulate ALS phenotype
- Zebrafish models: Motor neuron deficits with CHCHD10 knockdown
Diagnostic Testing
- Genetic testing: NGS panels for ALS/FTD genes
- Biochemical testing: Muscle biopsy for COX deficiency
- Imaging: MRI to rule out other causes
See Also
- [CHCHD10 Protein](/proteins/chchd10-protein)
- [ALS](/diseases/amyotrophic-lateral-sclerosis)
- [FTD](/diseases/frontotemporal-dementia)
- [Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction-pathway)
- [Motor Neuron Disease Mechanisms](/diseases/motor-neuron-disease)
- [Iron-Sulfur Cluster Biogenesis](/mechanisms/iron-sulfur-cluster-assembly)
Overview
Chchd10 Gene plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Background
The study of Chchd10 Gene 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.
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
- [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
- [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data
References
[Bannwarth S, et al, (2014) (2014)](https://doi.org/10.1093/brain/awu224)
[Johnson JO, et al, (2014) (2014)](https://doi.org/10.1016/j.neurobiolaging.2014.05.005)
[Strahm M, et al, (2015) (2015)](https://doi.org/10.1093/brain/aww016)
[Genin A, et al, (2016) (2016)](https://doi.org/10.1093/hmg/ddv259)
[Rouzier C, et al, (2016) (2016)](https://doi.org/10.1093/brain/awv295)
[Zhang X, et al, (2020) (2020)](https://doi.org/10.1038/s41419-020-02852-7)
[Wang T, et al, (2021) (2021)](https://doi.org/10.1523/JNEUROSCI.2049-20.2020)
[Penttilä S, et al, (2022) (2022)](https://doi.org/10.1016/j.nbd.2022.105720)
[Ajmone MA, et al, (2019) (2019)](https://doi.org/10.1002/humu.23838)
[Chaussenot R, et al, (2014) (2014)](https://doi.org/10.1016/j.neurobiolaging.2014.06.012)