{"entity":{"id":"erbb4","kind":"target","name":"HER4 (ERBB4)","aka":[],"tldr":"The fourth member of the HER family, hit by the irreversible pan-HER inhibitors afatinib, dacomitinib and neratinib along with EGFR and HER2. It has no approved drug of its own, and its role in cancer is less clear than that of its siblings.","summary":"ERBB4 (HER4) is a receptor tyrosine kinase activated by neuregulins that pairs with HER2 and other family members. Unlike EGFR and HER2 it is not an established oncogenic driver, and some studies link its expression to better outcomes in breast cancer. The irreversible pan-HER inhibitors afatinib and dacomitinib, approved for EGFR-mutant lung cancer, and neratinib, approved for HER2-positive breast cancer, inhibit ERBB4 as part of covering the whole family and preventing escape through HER2 or HER3 dimers. Rare ERBB4 mutations occur in melanoma and lung cancer but have no approved matched therapy.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/ERBB4","links":[{"label":"UniProt Q15303: ERBB4","url":"https://www.uniprot.org/uniprotkb/Q15303/entry"}],"tags":[],"related":[],"cancers":["nsclc","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["afatinib","dacomitinib","neratinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"ERBB4","role":[],"sources":[],"specificity":"tumour-associated","distribution":"few-types","specificityNote":"Tumour-associated overexpression: HPA finds the RNA cancer enhanced in cancer (Breast Invasive Carcinoma (TCGA)) and tissue enhanced in normal blood vessel, brain, fallopian tube, so the tumour and the normal tissue it comes from share the target and the medicine relies on the difference in level. HPA ERBB4: RNA tissue enhanced (blood vessel 8 nTPM, brain 8 nTPM, fallopian tube 11 nTPM); no normal tissue stained high; highest cancer staining pancreatic cancer (1 of 12 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Skin cancer (all types), Lung cancer (all types), Breast cancer (all types)); Open Targets associates it with 3 specific cancer types at or above 0.5 (non-small cell lung carcinoma, breast cancer, medullary thyroid gland carcinoma). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas ERBB4 tissue","url":"https://www.proteinatlas.org/ENSG00000178568-ERBB4/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas ERBB4 pathology","url":"https://www.proteinatlas.org/ENSG00000178568-ERBB4/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000178568 associations","url":"https://platform.opentargets.org/target/ENSG00000178568/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:3432","ensembl":"ENSG00000178568","uniprot":"Q15303","entrez":"2066","firstDescribed":1993,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Plowman G.D. et al, Proc. Natl. Acad. Sci. U.S.A, 1993, \"Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8383326/","biology":"Neuregulin receptor of the HER family; inhibited by pan-HER covalent inhibitors rather than by a dedicated drug.","whereFound":["EGFR-mutant non-small-cell lung cancer (as a pan-HER target)","HER2-positive breast cancer (as a pan-HER target)"],"targetClass":"kinase","prevalence":[{"cancerId":"melanoma","pct":19,"measure":"Somatic ERBB4 mutation, sequencing of 79 cutaneous metastatic melanomas","source":"https://doi.org/10.1038/ng.438","note":"Mutations increased kinase activity; mutant cells were sensitive to the ERBB inhibitor lapatinib"}]},"route":"/targets/erbb4/","neighbours":{"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"drug":[{"id":"afatinib","kind":"drug","name":"Afatinib","route":"/drugs/afatinib/"},{"id":"dacomitinib","kind":"drug","name":"Dacomitinib","route":"/drugs/dacomitinib/"},{"id":"neratinib","kind":"drug","name":"Neratinib","route":"/drugs/neratinib/"}],"paper":[{"id":"paper-yarden-sliwkowski-erbb-network-nrmcb-2001","kind":"paper","name":"Yarden and Sliwkowski 2001: untangling the ErbB signalling network","route":"/key-papers/paper-yarden-sliwkowski-erbb-network-nrmcb-2001/"}]}}