NCOA2
NCOA2 (Nuclear receptor coactivator 2) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Oesophageal cancer, Gastric & gastro-oesophageal junction cancer, Lung cancer and 5 more.
Overview
Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.
Open Targets scores its association with cancer at 0.70 (direct and indirect evidence; datatypes literature 0.95, genetic association 0.39, somatic mutation 0.85). IntOGen calls it a driver in 4 cohorts (2 activating, 2 loss-of-function), covering Oesophageal Adenocarcinoma, Lung Adenocarcinoma, Lung Squamous Cell Carcinoma, Stomach Adenocarcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · NCOA2 (Nuclear receptor coactivator 2) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Oesophageal cancer, Gastric & gastro-oesophageal junction cancer, Lung cancer and 5 more.
- 1 · What it is
NCOA2 (Nuclear receptor coactivator 2) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Oesophageal cancer, Gastric & gastro-oesophageal junction cancer, Lung cancer and 5 more.
- 2 · What goes wrong in cancer
Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1).
- 3 · How drugs use it
No product in this corpus aims at NCOA2 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Sources: HGNC HGNC:7669 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q15596 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000140396 (association with cancer (MONDO_0004992) 0.70; per-cancer scores at or above 0.5: oesophageal cancer 0.51, prostate cancer 0.52, sarcoma 0.56, breast cancer 0.56, lung cancer 0.57, chondrosarcoma 0.51 (GraphQL API, CC0)); IntOGen NCOA2 (driver in 4 cohorts (Act 2, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues. Critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression. Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3. Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer. Location: Nucleus (UniProt). Locus 8q13.3 (HGNC).
- Oesophageal cancer: Open Targets association 0.51 with oesophageal cancer (MONDO_0007576); IntOGen driver in 1 cohort (ESCA)
- Gastric & gastro-oesophageal junction cancer: IntOGen driver in 1 cohort (STAD)
- Lung cancer: Open Targets association 0.57 with lung cancer (MONDO_0008903)
- Breast cancer: Open Targets association 0.56 with breast cancer (MONDO_0007254)
- Sarcomas: Open Targets association 0.56 with sarcoma (MONDO_0005089)
- Prostate cancer: Open Targets association 0.52 with prostate cancer (MONDO_0008315)
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: IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"NCOA2" OR ABSTRACT:"NCOA2" OR TITLE:"nuclear receptor coactivator 2" OR ABSTRACT:"nuclear receptor coactivator 2" OR TITLE:"Nuclear receptor coactivator 2" OR ABSTRACT:"Nuclear receptor coactivator 2" OR TITLE:"SRC-2" OR ABSTRACT:"SRC-2" OR TITLE:"TIF2" OR ABSTRACT:"TIF2" OR TITLE:"GRIP1" OR ABSTRACT:"GRIP1") 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 NCOA2, not a curated reading list.
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