{"entity":{"id":"nrg1","kind":"target","name":"NRG1","aka":["neuregulin 1","Pro-neuregulin-1, membrane-bound isoform","NRG1-IT2"],"tldr":"NRG1 (Pro-neuregulin-1, membrane-bound isoform) is a protein on the cell surface. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker, a fusion partner and an antigen, and an approved or late-stage drug is recorded against it. Tied to Lung cancer, Thyroid cancer, Breast cancer and 5 more.","summary":"Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumour cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart.\n\nCIViC holds 9 clinical evidence items and 0 assertions across 3 variants, naming Lapatinib, Afatinib, Gefitinib and Erlotinib and others. Open Targets scores its association with cancer at 0.83 (direct and indirect evidence; datatypes affected pathway 0.92, literature 0.99, genetic association 0.70, somatic mutation 0.86, animal model 0.57). IntOGen calls it a driver in 3 cohorts (2 activating, 1 loss-of-function), covering Oesophageal Adenocarcinoma, Papillary Renal Cell Carcinoma, Stomach Adenocarcinoma. In OnCo, 1 product record names it (Zenocutuzumab).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:7997","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7997"},{"label":"UniProt Q02297","url":"https://www.uniprot.org/uniprotkb/Q02297/entry"},{"label":"NCBI Gene 3084","url":"https://www.ncbi.nlm.nih.gov/gene/3084"},{"label":"Ensembl ENSG00000157168","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000157168"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen","nrg1-fusion"],"cancers":["lung-cancer","thyroid","breast-cancer","colorectal","ovarian","head-and-neck","gastric","esophageal","pancreatic","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["zenocutuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":["gene-fusion"],"trials":["nct02912949"],"people":[],"bottlenecks":[],"keyPapers":["paper-philip-kras-wild-type-pancreatic-ccr-2022","paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018","paper-jones-nrg1-fusions-recurrent-actionable-kras-wild-type-pdac-ccr-2019","paper-enrgy-zenocutuzumab-nrg1-fusion-positive-cancer-nejm-2025","paper-jonna-nrg1-fusions-solid-tumours-ccr-2019","paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014"],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 12 therapies; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 9 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene; a membrane or secreted protein (UniProt keywords) that 1 antibody-based OnCo product name. Evidence tier \"approved-drug\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Pancreatic ductal adenocarcinoma: NRG1 fusions are found in 0.3 to 1% overall but in 1.3% of KRAS wild-type tumours and in every wild-type tumour of two whole-genome series (Heining 2018, Jones 2019; Philip 2022). Partners include ATP1B1, CD44 and NOTCH2 (cBioPortal pdac_msk_2024). Zenocutuzumab gave responses in 15 of 36 pancreatic patients, 42%, in eNRGy (Schram 2025); afatinib produced rapid responses before it. Detection needs RNA-based or intron-covering sequencing.","Lung cancer: rearranged in about 0.3% of cases, the highest incidence of any tumour type in a 21,858-sample RNA fusion series (Jonna 2019), and concentrated in invasive mucinous adenocarcinoma, the histology with no other driver (Fernandez-Cuesta 2014). The fusion presents the EGF-like domain of neuregulin 1 at the cell surface as a ligand for HER2-HER3 dimers, so it is treated with an antibody against the receptor pair rather than a kinase inhibitor, and it is the alteration most dependent on RNA-based testing."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"NRG1","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker","fusion-partner","antigen"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:7997","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7997","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q02297","url":"https://www.uniprot.org/uniprotkb/Q02297/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene NRG1","url":"https://civicdb.org/features/2593","note":"9 evidence items, 0 assertions, 3 variants; diseases: Lung Non-small Cell Carcinoma, Colorectal Cancer, Ovarian Cancer, Breast Cancer, Head And Neck Squamous Cell Carcinoma and 1 more (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000157168","url":"https://platform.opentargets.org/target/ENSG00000157168/associations","note":"association with cancer (MONDO_0004992) 0.83; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.67, gastric cancer 0.54, oesophageal cancer 0.51, thyroid cancer 0.64, neuroendocrine neoplasm 0.52, skin cancer 0.52 (GraphQL API, CC0)"},{"label":"IntOGen NRG1","url":"https://www.intogen.org/search?gene=NRG1","note":"driver in 3 cohorts (Act 2, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"lineage-antigen","distribution":"many-types","specificityNote":"Lineage antigen shared with normal monocytes: HPA blood lineage lineage enriched at or above 25 nTPM, and 1 antibody (Zenocutuzumab) aim at it, so normal cells of the lineage are hit too. HPA NRG1: RNA tissue enhanced (liver 16 nTPM); blood lineage lineage enriched (monocytes 54 nTPM); no normal tissue stained high; highest cancer staining lymphoma (3 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lung cancer (all types), Thyroid cancer, Breast cancer (all types), Colorectal cancer, Ovarian cancer, Head and neck squamous cell carcinoma, Gastric & gastro-oesophageal junction cancer and more); Open Targets associates it with 5 specific cancer types at or above 0.5 (lung adenocarcinoma, thyroid gland carcinoma, thyroid cancer, thyroid gland papillary carcinoma, non-small cell lung carcinoma). (Rule 5 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas NRG1 tissue","url":"https://www.proteinatlas.org/ENSG00000157168-NRG1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas NRG1 pathology","url":"https://www.proteinatlas.org/ENSG00000157168-NRG1/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000157168 associations","url":"https://platform.opentargets.org/target/ENSG00000157168/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7997","ensembl":"ENSG00000157168","uniprot":"Q02297","entrez":"3084","firstDescribed":1992,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Holmes W.E. et al, Science, 1992, \"Identification of heregulin, a specific activator of p185erbB2\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1350381/","biology":"Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumour cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. Binds to ERBB4. Binds to ERBB3. Location: Cell membrane; Secreted; Nucleus; Membrane (UniProt). Locus 8p12 (HGNC).","whereFound":["Lung cancer: Open Targets association 0.68 with lung cancer (MONDO_0008903)","Thyroid cancer: Open Targets association 0.64 with thyroid cancer (MONDO_0002108)","Breast cancer: Open Targets association 0.58 with breast cancer (MONDO_0007254); CIViC evidence names this disease","Colorectal cancer: CIViC evidence names this disease","Ovarian cancer: CIViC evidence names this disease","Head and neck squamous cell carcinoma: CIViC evidence names this disease","Pancreatic ductal adenocarcinoma: gene fusion (atp1b1-nrg1, cd44-nrg1 and others) 0.3-1%","Non-small-cell lung cancer: rearrangement, commonly cd74-nrg1, in invasive mucinous adenocarcinoma about 0.3%"],"targetClass":"surface-antigen","prevalence":[{"cancerId":"pancreatic","pct":"0.3-1","measure":"Gene fusion (ATP1B1-NRG1, CD44-NRG1 and others)","source":"https://www.cbioportal.org/study/summary?id=pdac_msk_2024","note":"cBioPortal structural variants: 6 of 2,336 samples, 0.26% (ATP1B1-NRG1 2, CD44-NRG1 1, NOTCH2-NRG1 1), in pdac_msk_2024 and 2 of 184, 1.1% (ATP1B1-NRG1, UBXN8-NRG1), in paad_tcga_pan_can_atlas_2018; 1.3% of 266 KRAS wild-type tumours (Philip 2022); recurrent in KRAS wild-type young adults, with ERBB inhibition giving remissions of liver metastases in 2 patients (Heining 2018); present in all 3 KRAS wild-type tumours among 47 whole genomes, with rapid responses to afatinib in 2 (Jones 2019). Zenocutuzumab gave responses in 15 of 36 pancreatic patients, 42%, in eNRGy (Schram 2025)."},{"cancerId":"nsclc","pct":0.3,"measure":"Rearrangement, commonly CD74-NRG1, in invasive mucinous adenocarcinoma","source":"https://doi.org/10.1158/1078-0432.CCR-19-0160","note":"25 of the non-small-cell lung cancers among 21,858 tumours profiled by anchored multiplex RNA sequencing carried an NRG1 fusion, 0.3% of the lung cases and the highest incidence of any tumour type in the series (Jonna 2019). cBioPortal structural variants: 7 of 2,422, 0.3%, in luad_mskcc_2023_met_organotropism; 2 of 232 in lung_nci_2022 (CD74-NRG1 and SLC3A2-NRG1); 2 of 2,621 in nsclc_ctdx_msk_2022. The fusion was discovered by transcriptome sequencing of 25 never-smoker adenocarcinomas, then found in 4 more of 102 driver-negative tumours, all of the invasive mucinous subtype (Fernandez-Cuesta 2014)."}]},"route":"/targets/nrg1/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"biomarker":[{"id":"nrg1-fusion","kind":"biomarker","name":"NRG1 gene fusion","route":"/biomarkers/nrg1-fusion/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"invasive-mucinous-adenocarcinoma-lung","kind":"cancer","name":"Invasive mucinous adenocarcinoma of the lung","route":"/cancers/invasive-mucinous-adenocarcinoma-lung/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"drug":[{"id":"zenocutuzumab","kind":"drug","name":"Zenocutuzumab","route":"/drugs/zenocutuzumab/"}],"term":[{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"}],"trial":[{"id":"nct02912949","kind":"trial","name":"A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)","route":"/trials/nct02912949/"}],"paper":[{"id":"paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014","kind":"paper","name":"CD74-NRG1 fusions in lung adenocarcinoma","route":"/key-papers/paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014/"},{"id":"paper-jonna-nrg1-fusions-solid-tumours-ccr-2019","kind":"paper","name":"Detection of NRG1 gene fusions in solid tumors","route":"/key-papers/paper-jonna-nrg1-fusions-solid-tumours-ccr-2019/"},{"id":"paper-enrgy-zenocutuzumab-nrg1-fusion-positive-cancer-nejm-2025","kind":"paper","name":"eNRGy: efficacy of zenocutuzumab in NRG1 fusion-positive cancer","route":"/key-papers/paper-enrgy-zenocutuzumab-nrg1-fusion-positive-cancer-nejm-2025/"},{"id":"paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018","kind":"paper","name":"Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer","route":"/key-papers/paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018/"},{"id":"paper-jones-nrg1-fusions-recurrent-actionable-kras-wild-type-pdac-ccr-2019","kind":"paper","name":"Jones 2019: NRG1 gene fusions are recurrent, clinically actionable rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma","route":"/key-papers/paper-jones-nrg1-fusions-recurrent-actionable-kras-wild-type-pdac-ccr-2019/"},{"id":"paper-philip-kras-wild-type-pancreatic-ccr-2022","kind":"paper","name":"Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma","route":"/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/"}]}}