ERBB2
Chr 17erb-b2 receptor tyrosine kinase 2
Also known as: CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19, NEU, NGL
This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ERBB2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Niraparib + Dostarlimab In BRCA Mutated Breast Cancer
ACTIVE NOT RECRUITINGHigh Definition Medicine for Solid Tumors Oncology
RECRUITINGIdentification of HER2-Positive Breast Cancer Molecular Characterization and Subtypes
NOT YET RECRUITINGProspective Study of the Prosigna Assay on Neoadjuvant Clinical Decision-making in Women With HR+/Her2- Breast Cancer
ACTIVE NOT RECRUITINGCAPRI 2 GOIM Study: Investigate the Efficacy and Safety of a Bio-marker Driven Cetuximab-based Treatment Regimen
ACTIVE NOT RECRUITINGPreoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer
ACTIVE NOT RECRUITINGTesting the Addition of an Anti-cancer Drug, Berzosertib, to the Usual Treatment (Radiation Therapy) for Chemotherapy-Resistant Triple-Negative and Estrogen and/or Progesterone Receptor Positive, HER2 Negative Breast Cancer
ACTIVE NOT RECRUITINGStudy of AMXT 1501 and DFMO in Combination With Standard Therapies in Advanced Solid Tumors
RECRUITINGAfrican Cancer Genome: GMD
RECRUITINGPHOENIX: QL1706 Plus Chemotherapy and Bevacizumab in AGA-Resistant, PD-L1 ≥50% Non-Squamous NSCLC
NOT YET RECRUITINGAdditional Support Program Via Text Messaging and Telephone-Based Counseling for Breast Cancer Patients Receiving Hormonal Therapy
ACTIVE NOT RECRUITINGImpact of Endocrine Therapy, Menstrual Cycle, PAM50, Ki67 on Treatment Decisions in HR+ and HER2- Breast Cancer
RECRUITINGExternal Resources
Links to major genomics databases and tools