ERBB2 Gene

HGNC Family	Receptor kinases, CD molecules (CD), Minor histocompatibility antigens
Name	erb-b2 receptor tyrosine kinase 2
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ERBB2 (also known as HER2/neu) is a member of the epidermal growth factor receptor family that lacks a known ligand yet adopts a fixed, “ligand‐activated” conformation that predisposes it to heterodimerize with other ErbB receptors, thereby potently activating downstream signaling cascades. Its overexpression in tumors such as breast and gastric cancers drives constitutive activation of the phosphatidylinositol 3‐kinase (PI3K)/AKT pathway, which in turn promotes cell proliferation, survival, and other oncogenic functions. Structural studies have revealed that the extracellular region of ERBB2 is uniquely configured to interact with partner receptors, a feature that is exploited by targeted monoclonal antibodies (e.g., trastuzumab and pertuzumab) to disrupt receptor dimerization and attenuate oncogenic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its classical role in driving tumor cell proliferation, ERBB2 overexpression can also modulate cellular metabolism; for example, it rescues the ATP deficiency observed in matrix-detached mammary epithelial cells by stabilizing epidermal growth factor receptor (EGFR) and promoting PI3K activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the context of immunotherapy, the efficacy of agents such as trastuzumab is partly mediated by antibody-dependent cellular cytotoxicity, a process influenced by host Fc receptor polymorphisms that affect the engagement of immune effector cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, regulatory mechanisms at the RNA level—for example, interactions with long noncoding RNAs like HOTAIR—can positively modulate ERBB2 expression and thereby contribute to the progression of gastric cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In breast cancer, the interplay between ERBB2 overexpression and other genetic alterations, such as PIK3CA mutations, further underscores its role in reinforcing the PI3K/AKT signaling axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " ERBB2-driven activation of this pathway can also influence cell cycle progression by modulating Akt-dependent phosphorylation events that result in cytosolic retention of the cyclin-dependent kinase inhibitor p27, thereby promoting tumor cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Importantly, the functions of ERBB2 are not confined to oncogenesis; signaling via this receptor tyrosine kinase is also essential for normal cardiac physiology. Cardiac-restricted deletion of ERBB2 leads to dilated cardiomyopathy, reflecting an indispensable role in maintaining cardiomyocyte function and overall heart integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these observations highlight the multifaceted role of ERBB2 in both normal physiology and cancer pathobiology, where its ability to regulate proliferation, survival, metabolic adaptation, and cell cycle control makes it a critical therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Luca Gianni, Tadeusz Pienkowski, Young-Hyuck Im, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lancet Oncol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S1470-2045(11)70336-9"}], "href": "https://doi.org/10.1016/S1470-2045(11"}, {"type": "t", "text": "70336-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22153890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22153890"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Thomas Holbro, Roger R Beerli, Francisca Maurer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1537685100"}], "href": "https://doi.org/10.1073/pnas.1537685100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12853564"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12853564"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zachary T Schafer, Alexandra R Grassian, Loling Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature08268"}], "href": "https://doi.org/10.1038/nature08268"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19693011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19693011"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Antonino Musolino, Nadia Naldi, Beatrice Bortesi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2007.14.8957"}], "href": "https://doi.org/10.1200/JCO.2007.14.8957"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18347005"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18347005"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xiang-Hua Liu, Ming Sun, Feng-Qi Nie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-13-92"}], "href": "https://doi.org/10.1186/1476-4598-13-92"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24775712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24775712"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lao H Saal, Karolina Holm, Matthew Maurer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472-CAN-04-3913"}], "href": "https://doi.org/10.1158/0008-5472-CAN-04-3913"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15805248"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15805248"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Incheol Shin, F Michael Yakes, Federico Rojo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm759"}], "href": "https://doi.org/10.1038/nm759"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12244301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12244301"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Steven A Crone, You-Yang Zhao, Lian Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ErbB2 is essential in the prevention of dilated cardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm0502-459"}], "href": "https://doi.org/10.1038/nm0502-459"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11984589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11984589"}]}]}]}
Synonyms	NEU, HER-2, MLN 19, CD340, TKR1, NGL, HER2, HER-2/NEU
Proteins	ERBB2_HUMAN
NCBI Gene ID	2064
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ERBB2 has 21,923 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 144 datasets.

Click the + buttons to view associations for ERBB2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ERBB2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by ERBB2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ERBB2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of ERBB2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of ERBB2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ERBB2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of ERBB2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of ERBB2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving ERBB2 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ERBB2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of ERBB2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ERBB2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of ERBB2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with ERBB2 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ERBB2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ERBB2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ERBB2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ERBB2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of ERBB2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with ERBB2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing ERBB2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ERBB2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ERBB2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ERBB2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ERBB2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ERBB2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ERBB2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with ERBB2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing ERBB2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ERBB2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ERBB2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ERBB2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ERBB2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ERBB2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ERBB2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate ERBB2 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ERBB2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ERBB2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ERBB2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ERBB2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with ERBB2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.