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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.
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.
CIViC 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).
In plain words · 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.
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.
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.
No product in this corpus aims at NRG1 yet. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
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.)
Sources: Human Protein Atlas NRG1 tissue; Human Protein Atlas NRG1 pathology; Open Targets ENSG00000157168 associations
First described 1992. Earliest sequence paper UniProt cites for the protein: Holmes W.E. et al, Science, 1992, "Identification of heregulin, a specific activator of p185erbB2". Source.
Sources: HGNC HGNC:7997 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q02297 (protein name, function text, keywords and locations (REST API)); CIViC gene NRG1 (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)); Open Targets ENSG00000157168 (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)); IntOGen NRG1 (driver in 3 cohorts (Act 2, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
RNA: tissue enhanced (liver 16 nTPM), detected in many normal tissues. Blood: lineage enriched (monocytes 54 nTPM).
No normal tissue stained high.
RNA cancer enhanced: Head and Neck Squamous Cell Carcinoma 26 pTPM.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Pancreatic ductal adenocarcinoma | 0.3-1% | Gene fusion (ATP1B1-NRG1, CD44-NRG1 and others) | 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). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 0.3% | Rearrangement, commonly CD74-NRG1, in invasive mucinous adenocarcinoma | 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). | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Every KRAS wild-type pancreatic cancer should be tested for NRG1 fusions because a specific, approved antibody now exists; zenocutuzumab is the first targeted drug approved for a pancreatic cancer driver.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
It put a number on how rare NRG1 fusions are and showed that heterogeneous partners make RNA-based testing the only reliable way to find them, which is the practical argument for adding a fusion panel to a driver-negative lung cancer work-up.
Together with the German MASTER report, this paper is why guidelines recommend comprehensive profiling with fusion detection in KRAS wild-type pancreatic cancer.
KRAS wild-type status should trigger fusion testing, ideally by RNA sequencing, because NRG1 fusions can be targeted by HER-family inhibitors and now by zenocutuzumab.
It identified a driver in the one lung histology that had none, and it defined a mechanism, ligand presentation, that requires an antibody against the receptor pair rather than a kinase inhibitor.
Query for this target: (TITLE:"NRG1" OR ABSTRACT:"NRG1" OR TITLE:"neuregulin 1" OR ABSTRACT:"neuregulin 1" OR TITLE:"Pro-neuregulin-1, membrane-bound isoform" OR ABSTRACT:"Pro-neuregulin-1, membrane-bound isoform" OR TITLE:"NRG1-IT2" OR ABSTRACT:"NRG1-IT2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about NRG1, not a curated reading list.
Shares Thyroid cancer, CIViC, IntOGen, Lung cancer (all types).
Shares Thyroid cancer, CIViC, IntOGen, Gastric & gastro-oesophageal junction cancer.
Shares Thyroid cancer, IntOGen, Gastric & gastro-oesophageal junction cancer, Lung cancer (all types).
Shares Thyroid cancer, CIViC, IntOGen, Gastric & gastro-oesophageal junction cancer.
Shares A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy), eNRGy: efficacy of zenocutuzumab in NRG1 fusion-positive cancer, Jones 2019: NRG1 gene fusions are recurrent, clinically actionable rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma, Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer.
Shares Thyroid cancer, IntOGen, Head and neck squamous cell carcinoma, Lung cancer (all types).
Shares eNRGy: efficacy of zenocutuzumab in NRG1 fusion-positive cancer, Jones 2019: NRG1 gene fusions are recurrent, clinically actionable rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma, Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer, Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma.
Shares Thyroid cancer, CIViC, IntOGen, Head and neck squamous cell carcinoma.