NSD2
NSD2 (Histone-lysine N-methyltransferase NSD2) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Multiple myeloma, Bladder & urothelial cancer, Lung cancer and 5 more.
Overview
Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2). Also monomethylates nucleosomal histone H3 at 'Lys-36' (H3K36me) in vitro. Does not trimethylate nucleosomal histone H3 at 'Lys-36' (H3K36me3).
CIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.64 (direct and indirect evidence; datatypes literature 0.98, genetic association 0.00, somatic mutation 0.83). IntOGen calls it a driver in 4 cohorts (3 activating, 1 loss-of-function), covering Acute Lymphoblastic Leukaemia, Burkitt Lymphoma, Plasma Cell Myeloma, Upper Tract Urothelial Carcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · NSD2 (Histone-lysine N-methyltransferase NSD2) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Multiple myeloma, Bladder & urothelial cancer, Lung cancer and 5 more.
- 1 · What it is
NSD2 (Histone-lysine N-methyltransferase NSD2) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Multiple myeloma, Bladder & urothelial cancer, Lung cancer and 5 more.
- 2 · What goes wrong in cancer
Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2). Also monomethylates nucleosomal histone H3 at 'Lys-36' (H3K36me) in vitro.
- 3 · How drugs use it
No product in this corpus aims at NSD2 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:12766 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O96028 (protein name, function text, keywords and locations (REST API)); CIViC gene NSD2 (1 evidence items, 0 assertions, 1 variants; diseases: Mantle Cell Lymphoma (GraphQL API, CC0)); Open Targets ENSG00000109685 (association with cancer (MONDO_0004992) 0.64; per-cancer scores at or above 0.5: colorectal cancer 0.51, head and neck squamous cell carcinoma 0.52, non-Hodgkin lymphoma 0.53, breast cancer 0.54, lung cancer 0.54, leukaemia 0.51 (GraphQL API, CC0)); IntOGen NSD2 (driver in 4 cohorts (Act 3, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2). Also monomethylates nucleosomal histone H3 at 'Lys-36' (H3K36me) in vitro. Does not trimethylate nucleosomal histone H3 at 'Lys-36' (H3K36me3). However, specifically trimethylates histone H3 at 'Lys-36' (H3K36me3) at euchromatic regions in embryonic stem (ES) cells. By methylating histone H3 at 'Lys-36', involved in the regulation of gene transcription during various biological processes. In ES cells, associates with developmental transcription factors such as SALL1 and represses inappropriate gene transcription mediated by histone deacetylation. Location: Nucleus; Chromosome; Cytoplasm; Nucleus, nucleolus (UniProt). Locus 4p16.3 (HGNC).
- Multiple myeloma: IntOGen driver in 1 cohort (PCM)
- Bladder & urothelial cancer: IntOGen driver in 1 cohort (UTUC)
- Lung cancer: Open Targets association 0.54 with lung cancer (MONDO_0008903)
- Breast cancer: Open Targets association 0.54 with breast cancer (MONDO_0007254)
- Non-Hodgkin lymphoma: Open Targets association 0.53 with non-Hodgkin lymphoma (MONDO_0018908)
- Head and neck squamous cell carcinoma: Open Targets association 0.52 with head and neck squamous cell carcinoma (MONDO_0010150)
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 3 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 1 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"NSD2" OR ABSTRACT:"NSD2" OR TITLE:"nuclear receptor binding SET domain protein 2" OR ABSTRACT:"nuclear receptor binding SET domain protein 2" OR TITLE:"Histone-lysine N-methyltransferase NSD2" OR ABSTRACT:"Histone-lysine N-methyltransferase NSD2" OR TITLE:"MMSET" OR ABSTRACT:"MMSET" OR TITLE:"KMT3G" OR ABSTRACT:"KMT3G" OR TITLE:"WHSC1" OR ABSTRACT:"WHSC1") 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 NSD2, not a curated reading list.
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