ERBB2 (HER2) Gene - Receptor Tyrosine-Protein Kinase
ERBB2: A key oncogene in breast and gastric cancers, encoding the HER2 receptor tyrosine kinase.
Gene Information Card
| Symbol | ERBB2 |
|---|---|
| Full Name | erb-b2 receptor tyrosine kinase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q12 |
| NCBI Gene ID | 2064 ncbi.nlm.nih.gov/gene/2064 |
| Ensembl ID | ENSG00000141736 |
| UniProt ID | P04626 |
| OMIM ID | 164870 |
| HGNC ID | 3430 |
| Aliases | HER2, HER-2, neu, NGL, TKR1, c-erb B2, CD340 |
Description
ERBB2 (HER2) is a proto-oncogene encoding a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This protein has no known direct ligand but forms heterodimers with other ligand-bound EGFR family members, leading to activation of downstream signaling pathways such as PI3K/AKT and MAPK/ERK. ERBB2 amplification and overexpression are oncogenic drivers in several cancers, most notably breast and gastric cancers, and are the target of therapies like trastuzumab and lapatinib.
Disease Associations
| Disease Name | Disease Description |
|---|---|
| Hereditary diffuse gastric cancer | Germline mutations in ERBB2 are rare; somatic amplification drives tumorigenesis via constitutive signaling. |
| Breast cancer | ERBB2 amplification/overexpression (HER2-positive) activates PI3K/AKT and MAPK pathways, promoting proliferation and survival. |
| Gastric cancer | ERBB2 amplification occurs in ~20% of gastric cancers, associated with poor prognosis and targeted by trastuzumab. |
| Ovarian cancer | ERBB2 amplification/overexpression in a subset of ovarian cancers contributes to oncogenic signaling. |
| Non-small cell lung cancer | ERBB2 mutations (e.g., exon 20 insertions) are oncogenic drivers in a small subset of NSCLC. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Breast | 12.5 | Medium |
| Stomach | 8.3 | Medium |
| Lung | 6.1 | Low |
| Ovary | 5.4 | Low |
| Kidney | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SK-BR-3 (breast cancer) | High | ERBB2-amplified cell line |
| BT-474 (breast cancer) | High | ERBB2-amplified cell line |
| MCF-7 (breast cancer) | Low | Non-amplified, low expression |
| NCI-N87 (gastric cancer) | High | ERBB2-amplified cell line |
| A549 (lung cancer) | Low | Wild-type expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Mutation site | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Val777Leu | Missense | <1% | Unknown functional impact; rare in cancer |
| p.Leu755Ser | Missense | <1% | Gain-of-function; associated with lung adenocarcinoma |
| p.Gly776delinsValCys | In-frame insertion | <1% | Gain-of-function; exon 20 insertion in NSCLC |
| p.Thr798Met | Missense | <1% | Likely gain-of-function; reported in breast cancer |
| Amplification | Copy number gain | ~20% in breast cancer | Oncogenic driver; leads to overexpression |
Mutation functional classification
Loss of Function (LOF)
Rare; not commonly described for ERBB2 in cancer.
Gain of Function (GOF)
Common; includes amplification and activating mutations (e.g., exon 20 insertions) that enhance kinase activity and downstream signaling.
Dominant Negative (DN)
Not typically reported for ERBB2; most mutations are gain-of-function.
View complete mutation data：ClinVar: https://www.clinvar.com/gene/2064 COSMIC: https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ERBB2
Gene Ontology (GO)
| • GO:0004714 - transmembrane receptor protein tyrosine kinase activity | • GO:0007169 - transmembrane receptor protein tyrosine kinase signaling pathway |
| • GO:0048011 - neurotrophin TRK receptor signaling pathway | • GO:0008284 - positive regulation of cell population proliferation |
| • GO:0016021 - integral component of membrane | • GO:0005886 - plasma membrane |
Pathways
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• MAPK signaling pathway (KEGG: hsa04010)
• ErbB signaling pathway (KEGG: hsa04012)
• Breast cancer pathway (KEGG: hsa05224)
• Gastric cancer pathway (KEGG: hsa05226)
Protein Summary
The ERBB2 protein (HER2) is a 185 kDa transmembrane receptor tyrosine kinase with an extracellular domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. It lacks a direct ligand but is the preferred dimerization partner for other EGFR family members. Upon heterodimerization, it autophosphorylates and activates downstream signaling cascades, including PI3K/AKT and MAPK/ERK, promoting cell growth, survival, and differentiation. Overexpression due to gene amplification leads to constitutive signaling and is a hallmark of aggressive HER2-positive breast and gastric cancers.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ERBB2 Knockout HEK293 Cell Line | EDC90180 | Human | 2064 | Details Get a Quote |
| ERBB2 Knockout HeLa Cell Line | EDJ-KQ17953 | Human | 2064 | Details Get a Quote |
| ERBB2 Knockout A-549 Cell Line | EDJ-KQ18140 | Human | 2064 | Details Get a Quote |
| ERBB2 Knockout HCT 116 Cell Line | EDJ-KQ19158 | Human | 2064 | Details Get a Quote |
| Erbb2 Knockout MC-38 Cell Line | EDJ-KZ218 | Mouse | 2064 | Details Get a Quote |
| ERBB2 (p.I655V) Point Mutation in HAP1 Cell Line | EDC03461 | Human | 2064 | Details Get a Quote |
| ERBB2 (c.2086-29G>A )Point Mutation in HAP1 Cell Line | EDC03462 | Human | 2064 | Details Get a Quote |
| ERBB2 Overexpression UM-UC-3 Stable Cell Line | EDC01672 | Human | 2064 | Details Get a Quote |
| ERBB2 Overexpression HEK293 Stable Cell Line | EDJ-GQ110 | Human | 2064 | Details Get a Quote |
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