# NRG1

Source: https://onco.cc/targets/nrg1/  
OnCo record `nrg1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: neuregulin 1; Pro-neuregulin-1, membrane-bound isoform; NRG1-IT2
- Tags: cancer-genes-wave
- Symbol: NRG1
- Class: surface-antigen
- 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).
- Where found: 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%

## 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.

## Sources

- HGNC HGNC:7997: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7997
- UniProt Q02297: https://www.uniprot.org/uniprotkb/Q02297/entry
- NCBI Gene 3084: https://www.ncbi.nlm.nih.gov/gene/3084
- Ensembl ENSG00000157168: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000157168

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- biomarkers: [NRG1 gene fusion](https://onco.cc/biomarkers/nrg1-fusion/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Invasive mucinous adenocarcinoma of the lung](https://onco.cc/cancers/invasive-mucinous-adenocarcinoma-lung/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Thyroid cancer](https://onco.cc/cancers/thyroid/)
- drugs: [Zenocutuzumab](https://onco.cc/drugs/zenocutuzumab/)
- terms: [Gene fusion](https://onco.cc/terms/gene-fusion/)
- trials: [A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)](https://onco.cc/trials/nct02912949/)
- key papers: [CD74-NRG1 fusions in lung adenocarcinoma](https://onco.cc/key-papers/paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014/), [Detection of NRG1 gene fusions in solid tumors](https://onco.cc/key-papers/paper-jonna-nrg1-fusions-solid-tumours-ccr-2019/), [eNRGy: efficacy of zenocutuzumab in NRG1 fusion-positive cancer](https://onco.cc/key-papers/paper-enrgy-zenocutuzumab-nrg1-fusion-positive-cancer-nejm-2025/), [Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer](https://onco.cc/key-papers/paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018/), [Jones 2019: NRG1 gene fusions are recurrent, clinically actionable rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-jones-nrg1-fusions-recurrent-actionable-kras-wild-type-pdac-ccr-2019/), [Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/)

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JSON: https://onco.cc/api/v1/entities/nrg1.json