# SETD2

Source: https://onco.cc/targets/setd2/  
OnCo record `setd2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

CIViC holds 3 clinical evidence items and 0 assertions across 2 variants, naming Akt Inhibitor MK2206, PI3Kbeta Inhibitor AZD8186, Samotolisib and Anti-PD1 Monoclonal Antibody and others. Open Targets scores its association with cancer at 0.81 (direct and indirect evidence; datatypes genetic literature 0.38, affected pathway 0.76, literature 0.99, genetic association 0.36, somatic mutation 0.94). IntOGen calls it a driver in 34 cohorts (1 activating, 33 loss-of-function), covering Acute Lymphoblastic Leukaemia, Renal Clear Cell Carcinoma, Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma, Oesophagogastric Adenocarcinoma, Ewing Sarcoma, Glioblastoma and others. In OnCo, 1 product record names it (Temsirolimus).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: SET domain containing 2, histone lysine methyltransferase; Histone-lysine N-methyltransferase SETD2; HIF-1; KIAA1732; FLJ23184; KMT3A
- Tags: cancer-genes-wave
- Symbol: SETD2
- Class: transcription
- 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 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)

## 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: CIViC lists 6 therapies; IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 33 cohorts; CIViC holds 3 clinical evidence items on its variants; UniProt keyword "DNA repair". Evidence tier "approved-drug" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Malignant Mesothelioma; Low-Grade Glioma, NOS.

## Sources

- HGNC HGNC:18420: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18420
- UniProt Q9BYW2: https://www.uniprot.org/uniprotkb/Q9BYW2/entry
- NCBI Gene 29072: https://www.ncbi.nlm.nih.gov/gene/29072
- Ensembl ENSG00000181555: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000181555

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Mesothelioma](https://onco.cc/cancers/mesothelioma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- drugs: [Temsirolimus](https://onco.cc/drugs/temsirolimus/)

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JSON: https://onco.cc/api/v1/entities/setd2.json