HDAC4 Gene

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HDAC4 Gene

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HDAC4 — Histone Deacetylase 4

Introduction

Hdac4 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.

<div class="infobox infobox-gene"> [@mcquown2011]
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Histone Deacetylase 4</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>HDAC4</td></tr>
<tr><td><strong>Full Name</strong></td><td>Histone Deacetylase 4</td></tr>
<tr><td><strong>Chromosome</strong></td><td>2q37.3</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[9759](https://www.ncbi.nlm.nih.gov/gene/9759)</td></tr>
<tr><td><strong>OMIM</strong></td><td>605314</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000113048</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P56524](https://www.uniprot.org/uniprot/P56524)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Alzheimer's Disease, Huntington's Disease, Parkinson's Disease, Brachydactyly, Cancer</td></tr>
</table>
</div>

Overview

...

HDAC4 — Histone Deacetylase 4

Introduction

Hdac4 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.

<div class="infobox infobox-gene"> [@mcquown2011]
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Histone Deacetylase 4</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>HDAC4</td></tr>
<tr><td><strong>Full Name</strong></td><td>Histone Deacetylase 4</td></tr>
<tr><td><strong>Chromosome</strong></td><td>2q37.3</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[9759](https://www.ncbi.nlm.nih.gov/gene/9759)</td></tr>
<tr><td><strong>OMIM</strong></td><td>605314</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000113048</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P56524](https://www.uniprot.org/uniprot/P56524)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Alzheimer's Disease, Huntington's Disease, Parkinson's Disease, Brachydactyly, Cancer</td></tr>
</table>
</div>

Overview

Mermaid diagram (expand to render)

HDAC4 ([Histone Deacetylase](/entities/hdac-enzymes) 4) is a Class IIa histone deacetylase that regulates gene expression through epigenetic modification and transcription factor interaction. It shuttles between the nucleus and cytoplasm, allowing it to regulate both transcriptional programs and cytoplasmic signaling pathways["@wang2019"]. HDAC4 is particularly important in the brain, where it regulates memory-related genes, neuronal development, and synaptic plasticity. Dysregulation of HDAC4 has been implicated in several neurodegenerative diseases, making it an attractive therapeutic target["@mcquown2011"].

Gene Structure

Chromosomal location: 2q37.3
Gene family: Histone deacetylase, Class IIa
Alternative splicing: Multiple isoforms

Protein Structure

Domain Organization

N-terminal domain: Transcription factor binding
Catalytic domain: HDAC activity
C-terminal domain: Nuclear localization signals

Key Features

Nuclear-cytoplasmic shuttling: Signal-dependent
Multiple phosphorylation sites: Regulation by kinases
Protein interactions: Broad binding profile

Molecular Function

Epigenetic Regulation

HDAC4 catalyzes histone deacetylation:

Histone modification: Removes acetyl groups from lysine tails

Chromatin remodeling: Promotes compact chromatin state

Transcriptional repression: Downregulates target genes

Transcriptional Regulation

Key Transcription Factor Interactions

MEF2: Muscle-specific transcription factor
REST: Neuronal gene repressor
Runx: Transcription factor family
[NF-κB](/entities/nf-kb): Inflammatory response

Signal-Dependent Regulation

Calcium signaling: CaMK-dependent phosphorylation
Stress responses: Cellular stress pathways
Hormonal signals: Nuclear hormone receptor crosstalk

Expression Pattern

Tissue Distribution

| Tissue | Expression Level |
|--------|-----------------|
| Brain | Very High |
| Heart | High |
| Skeletal Muscle | High |
| Lung | Moderate |
| Liver | Low |

Brain Regions

[Hippocampus](/brain-regions/hippocampus): Highest expression (CA1-CA3)
Cerebral [cortex](/brain-regions/cortex): All layers
Cerebellum: Purkinje cells
Basal ganglia: Moderate expression

Role in Disease

Alzheimer's Disease

Transcriptional dysregulation: Alters memory-related genes
Nuclear localization: Changed in AD [neurons](/entities/neurons)
HDAC inhibitors: Therapeutic benefit observed
Amyloid effects: [Aβ](/proteins/amyloid-beta) affects HDAC4 function[^3]

Huntington's Disease

Transcriptional dysfunction: Core pathological feature
Mutant [huntingtin](/proteins/huntingtin-protein): Alters HDAC4 localization
Therapeutic target: HDAC4 inhibitors under study
Therapeutic benefit: In mouse models

Parkinson's Disease

Dopaminergic neurons: HDAC4 affects survival
[α-Synuclein](/proteins/alpha-synuclein) pathology: Interactions studied
Therapeutic potential: Modulators in development

Other Conditions

Brachydactyly: HDAC4 mutations cause skeletal defects
Cancer: Dysregulated in various malignancies
Cardiovascular disease: Cardiac gene regulation

Therapeutic Approaches

HDAC Inhibitors

| Drug | Selectivity | Clinical Status |
|------|-------------|-----------------|
| Vorinostat | Pan-HDAC | Approved (CTCL) |
| Trichostatin A | Class I/IIa | Research |
| HDAC4-selective | HDAC4 | Preclinical |

Challenges

Brain penetration
Subtype selectivity
Side effect management

Research Directions

Selective inhibitors: Develop HDAC4-specific compounds

Mechanism studies: Understand disease-specific roles

Biomarkers: HDAC4 as disease marker

Gene therapy: AAV-mediated modulation

Animal Models

HDAC4 knockout: Developmental abnormalities
Conditional knockouts: Tissue-specific deletion
Transgenic models: Disease-associated changes

External Links

[NCBI Gene: HDAC4](https://www.ncbi.nlm.nih.gov/gene/9759)
[UniProt: P56524](https://www.uniprot.org/uniprot/P56524)
[Ensembl: ENSG00000113048](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000113048)
[Allen Brain Atlas: HDAC4](https://human.brain-map.org/microarray/search/show?search_term=HDAC4)

Background

The study of Hdac4 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.

References

Wang J, et al, HDAC4 in neurodegeneration (2019)

McQuown SC, et al, HDAC4 is a key regulator of memory (2011)

Pathway Diagram

The following diagram shows the key molecular relationships involving HDAC4 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

HDAC4

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-hdac4
kg_node_id	HDAC4
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-ca768dc4bdd5
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-hdac4'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

20

Outgoing

40

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

HDAC4 Gene

HDAC4 — Histone Deacetylase 4

Introduction

Overview

HDAC4 — Histone Deacetylase 4

Introduction

Overview

Gene Structure

Protein Structure

Domain Organization

Key Features

Molecular Function

Epigenetic Regulation

Transcriptional Regulation

Key Transcription Factor Interactions

Signal-Dependent Regulation

Expression Pattern

Tissue Distribution

Brain Regions

Role in Disease

Alzheimer's Disease

Huntington's Disease

Parkinson's Disease

Other Conditions

Therapeutic Approaches

HDAC Inhibitors

Challenges

Research Directions

Animal Models

See Also

External Links

Background

References

Pathway Diagram

💬 Discussion