OnCo

SETD2 (Histone-lysine N-methyltransferase SETD2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Renal cell carcinoma, Leukaemia, Non-Hodgkin lymphoma and 5 more. This dossier gathers the 0 products (0 approved), 0 trials, 0 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.

Biology

Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate. It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro. Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation. Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A. Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction. Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR). Location: Nucleus; Chromosome (UniProt). Locus 3p21.31 (HGNC).

Where it is found
  • Renal cell carcinoma: Open Targets association 0.70 with renal cell carcinoma (MONDO_0005086); IntOGen driver in 5 cohorts (CCRCC, PRCC, RCC)
  • Leukaemia: Open Targets association 0.66 with leukaemia (MONDO_0005059)
  • Non-Hodgkin lymphoma: Open Targets association 0.64 with non-Hodgkin lymphoma (MONDO_0018908)
  • Pancreatic ductal adenocarcinoma: IntOGen driver in 3 cohorts (PAAD, PANCREAS)
  • Mesothelioma: IntOGen driver in 3 cohorts (PLMESO)
  • Skin cancer: Open Targets association 0.61 with skin cancer (MONDO_0002898)
Class: transcription · Gene: SETD2 · Facts checked 2026-09-23 · Target page

External identifiers

Built from HGNC, Ensembl, UniProt and ChEMBL ids
SETD2SET domain containing 2, histone lysine methyltransferase · 3p21.31HGNCEnsemblUniProtAlphaFold DBOpen TargetsCIViCOncoKBCOSMICcBioPortalDepMapHuman Protein AtlasNCBI GeneOMIM

Products by modality and phase

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Resistance routes

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Companion diagnostics

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Preclinical models

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Literature

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Query for this target: (TITLE:"SETD2" OR ABSTRACT:"SETD2" OR TITLE:"SET domain containing 2, histone lysine methyltransferase" OR ABSTRACT:"SET domain containing 2, histone lysine methyltransferase" OR TITLE:"Histone-lysine N-methyltransferase SETD2" OR ABSTRACT:"Histone-lysine N-methyltransferase SETD2" OR TITLE:"HIF-1" OR ABSTRACT:"HIF-1" OR TITLE:"KIAA1732" OR ABSTRACT:"KIAA1732" OR TITLE:"FLJ23184" OR ABSTRACT:"FLJ23184") 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 SETD2, not a curated reading list.

Export

The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/setd2.json. Licence CC BY-NC 4.0.