ERBB4 Gene

ERBB4 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ERBB4 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ERBB4</td>
</tr>
<tr>
<td class="label">Gene Name</td>
<td>Erb-B2 Receptor Tyrosine Kinase 4</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>HER4, v-erb-a erythroblastic leukemia viral oncogene homolog 4</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>2q34</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>2065</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q15303</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000178668</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>EGFR/ERBB family</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~180 kDa (full-length)</td>
</tr>
<tr>
<td class="label">Amino Acids</td>
<td>1308</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Neuregulin</td>
<td>ERBB4 agonist</td>
</tr>
<tr>
<td class="label">Anti-ERBB4 antibodies</td>
<td>Block signaling</td>
</tr>
<tr>
<td class="label">Tyrosine kinase inhibitors</td>
<td>Inhibit activity</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Enhance signaling</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als"

...

ERBB4 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ERBB4 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ERBB4</td>
</tr>
<tr>
<td class="label">Gene Name</td>
<td>Erb-B2 Receptor Tyrosine Kinase 4</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>HER4, v-erb-a erythroblastic leukemia viral oncogene homolog 4</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>2q34</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>2065</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q15303</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000178668</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>EGFR/ERBB family</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~180 kDa (full-length)</td>
</tr>
<tr>
<td class="label">Amino Acids</td>
<td>1308</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Neuregulin</td>
<td>ERBB4 agonist</td>
</tr>
<tr>
<td class="label">Anti-ERBB4 antibodies</td>
<td>Block signaling</td>
</tr>
<tr>
<td class="label">Tyrosine kinase inhibitors</td>
<td>Inhibit activity</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Enhance signaling</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/anxiety" style="color:#ef9a9a">Anxiety</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">83 edges</a></td>
</tr>
</table>

Introduction

Erbb4 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.

Overview

ERBB4 (Erb-B2 Receptor Tyrosine Kinase 4), also known as HER4, is a member of the epidermal growth factor receptor (EGFR/ERBB) family of receptor tyrosine kinases. ERBB4 is a crucial signaling receptor in the brain, involved in neural development, synaptic plasticity, and neuronal survival. The gene is located on chromosome 2q34 and encodes a 1308-amino acid protein. [@mei2008]

Gene Information

Protein Structure

ERBB4 is a receptor tyrosine kinase with multiple isoforms:

• Extracellular domain: Four ligand-binding subdomains (I-IV)
• Transmembrane domain: Single pass helix
• Intracellular tyrosine kinase domain: Catalytic activity
• C-terminal tail: Multiple phosphorylation sites

Isoforms

ERBB4 has multiple isoforms due to alternative splicing:

• Cytoplasmic isoforms: CYT-1, CYT-2 (differ in C-terminus)
• Soluble isoforms: Produced by proteolytic cleavage
• JMa and JMb: Extracellular splicing variants

Normal Function

Receptor Signaling

ERBB4 functions as a receptor tyrosine kinase:

Binds neuregulin (NRG) ligands

Dimerizes (homodimer or heterodimer)

Autophosphorylates tyrosine residues

Activates downstream signaling cascades

Key Signaling Pathways

• PI3K/AKT: Cell survival, metabolism
• MAPK/ERK: Cell proliferation, differentiation
• STAT: Gene transcription
• PLCγ: Calcium signaling

Neuronal Functions

In the brain, ERBB4:

• Regulates neural development
• Controls synapse formation
• Mediates hippocampal plasticity
• Supports neuronal survival
• Modulates GABAergic signaling

Role in Neurodegeneration

Alzheimer's Disease

ERBB4 in AD:

• Elevated in AD brains
• Links [Aβ](/proteins/amyloid-beta) toxicity to signaling
• May have neuroprotective role
• Neuregulin-ERBB4 signaling affected
• Synaptic function modulation
• Therapeutic target potential

Parkinson's Disease

In PD:

• Expressed in dopaminergic neurons
• Neuregulin protection studies
• May affect [LRRK2](/entities/lrrk2) signaling
• Neurotrophic factor connections
• Gene variants under investigation

Schizophrenia

ERBB4 strongly associated with schizophrenia:

• Genetic risk factor identified
• Altered expression in schizophrenic brain
• Affects synaptic function
• Neuregulin-ERBB4 pathway dysregulated
• GABAergic interneuron development
• Therapeutic target interest

Other Disorders

• Epilepsy: Altered expression
• Autism: Genetic associations
• Bipolar disorder: GWAS signals

Therapeutic Implications

Drug Targets

Therapeutic Strategies

• Neuregulin delivery
• ERBB4 modulation
• Downstream pathway targeting
• Combination approaches

Gene Expression

• High in: Brain ([cortex](/brain-regions/cortex), hippocampus), heart, mammary gland
• Development: Important in neurodevelopment
• Adult: Maintained in specific brain regions
• Cell types: [Neurons](/entities/neurons), [astrocytes](/entities/astrocytes), oligodendrocytes

Animal Models

• Knockout mice: Embryonic/neonatal lethal
• Conditional knockouts: Brain-specific studies
• Transgenic overexpression: Neurological phenotypes
• Neuregulin mutants: Synaptic deficits

Research Directions

• Understanding isoform-specific functions
• Brain-penetrant modulators
• Biomarker development
• Gene therapy approaches
• Neuregulin-ERBB4 pathway modulation

Background

The study of Erbb4 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.

See Also

• ERBB4 Protein - Protein product
• EGFR/ERBB Family - Receptor family
• Neuregulin - ERBB4 ligand
• [Alzheimer's Disease](/diseases/al- [Parkinson's Disease](/diseases/parkinsons-disease) in AD
• [Parkinson's Disease](/diseases/parkinsons-disease) Neurotrophic factors
• Schizophrenia - Genetic association

External Links

• [NCBI Gene: ERBB4](https://www.ncbi.nlm.nih.gov/gene/2065)
• [UniProt: Q15303](https://www.uniprot.org/uniprot/Q15303)
• [GeneCards: ERBB4](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ERBB4)
• [Human Protein Atlas: ERBB4](https://www.proteinatlas.org/gene/ERBB4)

References

Yarden Y, Sliwkowski MX, (2001) (2001)

Mei L, Xiong WC, (2008) (2008)

Law AJ, et al, (2007) (2007)

Chan CB, Ye K, (2012) (2012)

Hahn CG, et al, (2006) (2006)

Cooper MA, Koleske AJ, (2014) (2014)

Pathway Diagram

The following diagram shows the key molecular relationships involving ERBB4 Gene discovered through SciDEX knowledge graph analysis: