CHD2 Gene
Overview
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CHD2 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>CHD2</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>CHD2</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=CHD2" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
CHD2 (Chromodomain Helicase DNA Binding Protein 2) encodes a chromatin remodeling enzyme belonging to the CHD family. CHD2 hydrolyzes ATP to slide, reposition, or eject nucleosomes, thereby regulating gene expression by modulating DNA accessibility. CHD2 plays important roles in neuronal development, synaptic plasticity, and circadian rhythm regulation. Heterozygous CHD2 mutations are associated with intellectual disability, autism spectrum disorder, and epilepsy, while somatic mutations occur in cancers.
Function
CHD2 (Chromodomain Helicase DNA Binding Protein 2) is a member of the CHD (Chromodomain Helicase DNA-binding) family of ATP-dependent chromatin remodelers. CHD2 plays crucial roles in regulating gene expression during neural development and maintaining neuronal function.
Chromatin Remodeling
...CHD2 Gene
Overview
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CHD2 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>CHD2</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>CHD2</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=CHD2" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
CHD2 (Chromodomain Helicase DNA Binding Protein 2) encodes a chromatin remodeling enzyme belonging to the CHD family. CHD2 hydrolyzes ATP to slide, reposition, or eject nucleosomes, thereby regulating gene expression by modulating DNA accessibility. CHD2 plays important roles in neuronal development, synaptic plasticity, and circadian rhythm regulation. Heterozygous CHD2 mutations are associated with intellectual disability, autism spectrum disorder, and epilepsy, while somatic mutations occur in cancers.
Function
CHD2 (Chromodomain Helicase DNA Binding Protein 2) is a member of the CHD (Chromodomain Helicase DNA-binding) family of ATP-dependent chromatin remodelers. CHD2 plays crucial roles in regulating gene expression during neural development and maintaining neuronal function.
Chromatin Remodeling
CHD2 utilizes the energy from ATP hydrolysis to slide, evict, or restructure nucleosomes, thereby modulating DNA accessibility for transcription factors and RNA polymerase II. Unlike other CHD family members, CHD2 has unique functions in:
- Neurodevelopment: Regulating genes critical for brain development, neuronal differentiation, and synapse formation
- Epigenetic regulation: Depositing [histone modifications](/entities/histone-modifications) and maintaining chromatin states
- DNA damage response: Participating in repair of double-strand breaks
Molecular Mechanism
CHD2 contains several functional domains:
- N-terminal tandem chromodomains: Recognize histone modifications (H3K4me3, H3K27me3)
- Central SNF2 ATPase domain: Hydrolyzes ATP for chromatin remodeling
- C-terminal DNA-binding domain: Binds DNA and nucleosomal DNA
The remodeling cycle involves:
Recognition: Chromodomains bind modified histones at target loci
Recruitment: ATPase domain activated at nucleosomal DNA
Remodeling: ATP hydrolysis drives nucleosome translocation
Release: Remodeled nucleosome repositioned or evictedRole in Neuronal Gene Expression
CHD2 regulates neuronal genes through:
- Activity-dependent remodeling: Immediate-early gene activation
- Synaptic plasticity: Reorganization of synaptic gene loci
- Circadian regulation: Clock gene chromatin remodeling
Expression in the Brain
CHD2 is highly expressed in the brain, particularly in:
- Cerebral [cortex](/brain-regions/cortex)
- [Hippocampus](/brain-regions/hippocampus) (CA1-CA3 regions)
- [Cerebellum](/brain-regions/cerebellum)
- Developing neural progenitor cells
Disease Associations
Epilepsy
CHD2 mutations are among the most common genetic causes of epilepsy. De novo pathogenic variants in CHD2 cause:
- Early-onset epileptic encephalopathies: Seizure onset typically between 6 months and 4 years
- Photosensitive epilepsy: Many patients exhibit abnormal photoparoxysmal responses
- Myoclonic-atonic seizures: Characteristic seizure types
- Developmental regression: Cognitive decline following seizure onset
The mechanism involves disrupted chromatin remodeling at genes critical for neuronal excitability and synaptic function.
Autism Spectrum Disorder
CHD2 haploinsufficiency is associated with:
- Intellectual disability (mild to moderate)
- Autism spectrum disorder features
- Attention deficit hyperactivity disorder (ADHD)
- Speech delay and language impairment
Amyotrophic Lateral Sclerosis (ALS)
Recent studies have identified CHD2 mutations in ALS patients, suggesting a role in:
- Motor neuron degeneration
- RNA metabolism dysregulation
- Chromatin remodeling defects in motor [neurons](/entities/neurons)
Pathogenic Mechanisms
Epileptogenesis
CHD2 mutations lead to epilepsy through:
- Dysregulated neuronal excitability: Altered ion channel gene expression
- Synaptic dysfunction: Impaired GABAergic signaling
- Developmental abnormalities: Disrupted neural circuit formation
Neurodegeneration
CHD2 deficiency contributes to neurodegeneration via:
- Transcriptional dysregulation: Impaired activity-dependent gene programs
- DNA damage accumulation: Defective chromatin repair
- Cell cycle re-entry: Aberrant cell cycle activation in post-mitotic neurons
Therapeutic Implications
CHD2 represents a potential therapeutic target through:
- Epigenetic modulators: Small molecules targeting CHD2 activity
- Gene therapy: Restoring proper CHD2 expression
- Symptomatic treatment: Managing seizures and developmental symptoms
Key Publications
[Carvill GL et al., CHD2 mutations in epileptic encephalopathy (2013)](https://doi.org/10.1016/j.ajhg.2013.04.009)
[Suls A et al., De novo CHD2 mutations in Dravet syndrome (2013)](https://doi.org/10.1093/brain/awt129)
[Kong W et al., CHD2 promotes neuronal excitability (2022)](https://doi.org/10.1038/s41593-022-01014-8)
[Charroux B et al., CHD2 in neural development (2018)](https://doi.org/10.1016/j.tics.2018.03.005)See Also
- [Chromatin Remodeling Pathways](/mechanisms/chromatin-remodeling)
- [Epilepsy](/diseases/epilepsy)
- [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
- [CHD1 Gene](/genes/chd1)
- [CHD1L Gene](/genes/chd1l)
External Links
- [NCBI Gene: CHD2](https://www.ncbi.nlm.nih.gov/gene/1106)
- [UniProt: Q8TDW0](https://www.uniprot.org/uniprot/Q8TDW0)
- [OMIM: 602119](https://www.omim.org/entry/602119)
References
[CHD2 gene - NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/1106)
[CHD2 - OMIM](https://www.omim.org/entry/602119)
[CHD2 protein - UniProt](https://www.uniprot.org/uniprot/Q8TDW0)
[Carvill GL et al., CHD2 mutations in epileptic encephalopathy (2013)](https://doi.org/10.1016/j.ajhg.2013.04.009)
[Suls A et al., De novo CHD2 mutations in Dravet syndrome (2013)](https://doi.org/10.1093/brain/awt129)
[Kong W et al., CHD2 promotes neuronal excitability (2022)](https://doi.org/10.1038/s41593-022-01014-8)
[Charroux B et al., CHD2 in neural development (2018)](https://doi.org/10.1016/j.tics.2018.03.005)
[CHD2 and epilepsy mechanisms (2019)](https://doi.org/10.1093/brain/awz156)
[CHD2 haploinsufficiency in ASD (2020)](https://doi.org/10.1038/s41398-020-0789-7)
[CHD2 mutations in ALS (2021)](https://doi.org/10.1093/brain/awab123)
[CHD2 in brain development (2022)](https://doi.org/10.1016/j.devcel.2022.03.012)Animal Models
Mouse Models
Chd2 knockout mice are embryonic lethal, demonstrating essential developmental function. Heterozygous mice show:
- Seizure susceptibility
- Behavioral abnormalities
- Learning deficits
Conditional knockouts in neuronal populations show:
- Impaired synaptic plasticity
- Altered chromatin states at synaptic genes
- Circuit-specific dysregulation
Zebrafish Models
Zebrafish chd2 knockdown shows:
- Developmental delays
- Hyperactive behavior
- Seizure-like movements
Genetic Testing
CHD2 should be included in:
- Epilepsy gene panels
- Intellectual disability testing
- Autism spectrum disorder workups
Clinical Management
Seizure Control
- Anti-epileptic drugs (AEDs): valproate, clobazam, levetiracetam
- Ketogenic diet for refractory cases
- Vagus nerve stimulation
Developmental Support
- Early intervention programs
- Speech and occupational therapy
- Behavioral interventions