{"entity":{"id":"nsd2","kind":"target","name":"NSD2","aka":["nuclear receptor binding SET domain protein 2","Histone-lysine N-methyltransferase NSD2","MMSET","KMT3G","WHSC1"],"tldr":"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.","summary":"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).\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:12766","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12766"},{"label":"UniProt O96028","url":"https://www.uniprot.org/uniprotkb/O96028/entry"},{"label":"NCBI Gene 7468","url":"https://www.ncbi.nlm.nih.gov/gene/7468"},{"label":"Ensembl ENSG00000109685","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000109685"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["multiple-myeloma","urothelial","lung-cancer","breast-cancer","non-hodgkin-lymphoma","head-and-neck","leukaemia","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"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: 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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"NSD2","role":["oncogene-driver","tumour-suppressor","biomarker","fusion-partner"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:12766","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12766","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt O96028","url":"https://www.uniprot.org/uniprotkb/O96028/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene NSD2","url":"https://civicdb.org/features/6107","note":"1 evidence items, 0 assertions, 1 variants; diseases: Mantle Cell Lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000109685","url":"https://platform.opentargets.org/target/ENSG00000109685/associations","note":"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)"},{"label":"IntOGen NSD2","url":"https://www.intogen.org/search?gene=NSD2","note":"driver in 4 cohorts (Act 3, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance) and a fusion partner (UniProt records a translocation), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA NSD2: RNA low tissue specificity; high antibody staining in 13 normal tissues; highest cancer staining colorectal cancer (10 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Multiple myeloma, Bladder & urothelial cancer, Lung cancer (all types), Breast cancer (all types), Lymphoma, Head and neck squamous cell carcinoma, Leukaemia and more); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt O96028","url":"https://www.uniprot.org/uniprotkb/O96028/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene NSD2","url":"https://civicdb.org/features/6107","note":"1 evidence items, 0 assertions, 1 variants; diseases: Mantle Cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen NSD2","url":"https://www.intogen.org/search?gene=NSD2","note":"driver in 4 cohorts (Act 3, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas NSD2 tissue","url":"https://www.proteinatlas.org/ENSG00000109685-NSD2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000109685 associations","url":"https://platform.opentargets.org/target/ENSG00000109685/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:12766","ensembl":"ENSG00000109685","uniprot":"O96028","entrez":"7468","firstDescribed":1998,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Chesi et al, Blood, 1998, \"The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9787135/","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).","whereFound":["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)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/nsd2/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}]}}