| CHCHD10 — Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10 | |
|---|---|
| Symbol | CHCHD10 |
| Full Name | Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 10 |
| Chromosome | 22q11.23 |
| NCBI Gene | 400916 |
| Ensembl | ENSG00000250479 |
| OMIM | 615903 |
| UniProt | Q8WYQ3 |
| Diseases | ALS, FTD, Mitochondrial Myopathy |
| Expression | Motor cortex, Spinal cord, Mitochondria (widespread) |
| Key Mutations | |
| S59L R15L G66V G58R P34S |
|
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.
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). 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). The gene is catalogued as NCBI Gene ID 400916 and OMIM 615903.
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). Loss of CHCHD10 function leads to cristae disorganization, impaired respiratory chain activity, and reduced ATP production.
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).
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).
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.
CHCHD10 mutations produce a remarkably broad phenotypic spectrum:
| Mutation | Disease Phenotype | Mechanism |
|---|---|---|
| S59L | ALS-FTD, myopathy, cardiomyopathy | Gain-of-function through toxic amyloid fibril formation (Zhou et al., 2024); 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 |
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.
Page expanded by NeuroWiki quality review. Last updated: 2026-02-27.