ERBB4 Gene
Erb-B2 Receptor Tyrosine Kinase 4
Gene Information Card
| Symbol | ERBB4 |
|---|---|
| Full Name | Erb-B2 Receptor Tyrosine Kinase 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q34 |
| NCBI Gene ID | 2066 ncbi.nlm.nih.gov/gene/2066 |
| Ensembl ID | ENSG00000178568 |
| UniProt ID | Q15303 |
| OMIM ID | 600543 |
| HGNC ID | 3432 |
| Aliases | HER4, p180erbB4, c-erbB-4 |
Description
ERBB4 (Erb-B2 Receptor Tyrosine Kinase 4) is a member of the epidermal growth factor receptor (EGFR/ErbB) family of receptor tyrosine kinases. It encodes a transmembrane glycoprotein that binds and is activated by neuregulins and other EGF-like ligands. Upon ligand binding, ERBB4 homodimerizes or heterodimerizes with other ErbB family members, leading to autophosphorylation and activation of downstream signaling pathways, including MAPK, PI3K/AKT, and JAK/STAT cascades. ERBB4 is involved in cell proliferation, differentiation, migration, and apoptosis, and plays critical roles in development of the nervous system, heart, and mammary gland.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (breast, lung, colorectal, gastric) | Somatic mutations and altered expression contribute to oncogenic signaling via constitutive activation or impaired regulation | NCBI Gene, COSMIC, ClinVar |
| Schizophrenia | Genetic variants and altered ERBB4 signaling in the brain affect neurodevelopment and synaptic plasticity | OMIM, NCBI Gene |
| Amyotrophic lateral sclerosis (ALS) | Rare variants and dysregulated ERBB4 expression in motor neurons linked to disease susceptibility | ClinVar, NCBI Gene |
| Dilated cardiomyopathy | Loss-of-function mutations impair cardiac development and contractile function | OMIM, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 18.5 | High |
| Heart | 12.3 | Medium |
| Breast | 9.8 | Medium |
| Lung | 6.2 | Low |
| Colon | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | High expression |
| A549 (lung cancer) | 8.7 | Moderate expression |
| HEK293 (embryonic kidney) | 5.3 | Low expression |
| SH-SY5Y (neuroblastoma) | 12.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Glu317Lys | Missense | 0.5% in breast cancer | Altered ligand binding and signaling |
| p.Arg1057Trp | Missense | 0.3% in schizophrenia | Impaired receptor trafficking |
| p.Val1051Ile | Missense | 0.2% in ALS | Reduced kinase activity |
| c.2340_2341insA | Frameshift | <0.1% in colorectal cancer | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the kinase domain or disrupt ligand binding, leading to reduced signaling; observed in dilated cardiomyopathy and some cancers.
Gain of Function (GOF)
Missense mutations in the kinase domain that increase autophosphorylation and downstream signaling, associated with oncogenic transformation in breast and lung cancers.
Dominant Negative (DN)
Mutations that produce truncated receptors lacking kinase activity but retaining dimerization capacity, interfering with wild-type ERBB4 and other ErbB family members.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ErbB signaling pathway (KEGG: hsa04012)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• MAPK signaling pathway (KEGG: hsa04010)
• Neuregulin signaling (Reactome: R-HSA-1227986)
Protein Summary
ERBB4 (HER4) is a 180 kDa transmembrane receptor tyrosine kinase composed of an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. It is activated by neuregulins (NRG1-4) and heparin-binding EGF-like ligands. Alternative splicing generates multiple isoforms with distinct juxtamembrane and cytoplasmic domains, influencing signaling specificity and susceptibility to proteolytic cleavage. The receptor undergoes regulated intramembrane proteolysis (RIP) to release an intracellular domain that can translocate to the nucleus and modulate transcription. ERBB4 is essential for normal development of the heart, nervous system, and mammary gland, and its dysregulation is implicated in cancer, neuropsychiatric disorders, and cardiomyopathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ERBB4 Knockout HEK293 Cell Line | EDJ-KQ655 | Human | 2066 | Details Get a Quote |
| ERBB4 Knockout HeLa Cell Line | EDJ-KQ19161 | Human | 2066 | Details Get a Quote |
| ERBB4 Knockout A-549 Cell Line | EDJ-KQ61650 | Human | 2066 | Details Get a Quote |
| ERBB4 Knockout HCT 116 Cell Line | EDJ-KQ70130 | Human | 2066 | Details Get a Quote |
