Gene

ERBB4

erb-b2 receptor tyrosine kinase 4

Explore in graph →CI-GENE-00044907HGNC:3432 ENSG00000178568 NCBI 2066 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (10)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–10 of 10 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
ERBB4 Fusion1
Mobocertinib + Osimertinib + Tarloxotinib + Trastuzumab DeruxtecanSequential	Lung Adenocarcinoma	Predictive	C

Cohorts

Alteration frequency by cohort (200)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved200 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Cutaneous Squamous Cell Carcinoma (MD Anderson, Clin Cancer Res 2014) cscc_hgsc_bcm_2014	Skin Squamous Cell Carcinoma	Ssm

Literature

Linked publications (3)

25 per page, newest first.

pubmedPublishedShowing 1–3 of 3 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4.
· Nat Genet · 2009 · PMID 19718025 · validated civic_curation pubmed
Receptor tyrosine kinase ERBB4 mediates acquired resistance to ERBB2 inhibitors in breast cancer cells.
· Cell Cycle · 2015 · PMID 25590338 · validated civic_curation pubmed
Nuclear HER4 mediates acquired resistance to trastuzumab and is associated with poor outcome in HER2 positive breast cancer.
· Oncotarget · 2014 · PMID 25153719 · validated civic_curation pubmed

ERBB4 EXPRESSION3
(prognostic)	HER2-Positive Breast CarcinomaALIAS	Prognostic	B	Supports Poor Outcome	3	submitted	EID1961 Preventing HER4 cleavage by a γ-secretase inhibitor and inhibiting HER4 tyrosine kinase activity by neratinib decreased trastuzumab-induced HER4 nuclear translocation and enhanced trastuzumab response… (full text at CIViC) PMID 25153719 · Mohd Nafi et al., 2014 · Open in CIViC	civic
Lapatinib	Malignant Breast Neoplasm	Predictive	D	Supports Resistance	3	accepted	EID869 ERBB4 protein expression was identified in breast cancer cell lines with acquired lapatinib resistance. Genetic ablation of ERBB4 (not ERBB1-3) led to apoptosis in trastuzumab- and lapatinib resistant… (full text at CIViC) PMID 25590338 · Canfield et al., 2015 · Open in CIViC	civic
Trastuzumab	HER2-Positive Breast CarcinomaALIAS	Predictive	D	Supports Resistance	2	accepted	EID868 siRNA knockdown of HER4 or inhibition with neratinib enhanced trastuzumab response in breast cancer cell lines. PMID 25153719 · Mohd Nafi et al., 2014 · Open in CIViC	civic

ERBB4 G1109C3
(oncogenic)	Malignant NeoplasmALIAS	Oncogenic	D	Supports Oncogenicity	4	submitted	EID9677 Multiple retrospective preclinical experiments were investigating the functional role of ERBB4 (HER4) G1109C mutation in various cell lines. HEK293 and NIH3T3 cell lines expressing either ERBB4 (HER4)… (full text at CIViC) PMID 27207775 · Nakamura et al., 2016 · Open in CIViC	civic
Afatinib	Head and Neck Squamous Cell Carcinoma	Predictive	D	Supports Sensitivity Response	4	submitted	EID9676 This retrospective preclinical study assessed the efficacy of afatinib towards head-and-neck squamous cell carcinoma (HNSCC) human cell lines expressing ERBB4 (HER4) G1109C mutation. According to the … (full text at CIViC) PMID 27207775 · Nakamura et al., 2016 · Open in CIViC	civic
Erlotinib	Head and Neck Squamous Cell Carcinoma	Predictive	D	Supports Resistance	—	submitted	EID4809 In an in vitro study, a head and neck squamous cell carcinoma cell line SAS expressing ERBB4 (HER4) G1109C was associated with insensitivity to erlotinib treatment (IC50=1.47uM). Resistance was determ… (full text at CIViC) PMID 27207775 · Nakamura et al., 2016 · Open in CIViC	civic