NRG1
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.
Overview
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).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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.
External identifiers
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)
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).
- 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
Notes
top- 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.
Latest papers
topQuery 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.
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