SETDB1
SETDB1 (Histone-lysine N-methyltransferase SETDB1) 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 Breast cancer, Colorectal cancer, Hepatocellular carcinoma and 5 more.
Overview
Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes.
IntOGen calls it a driver in 8 cohorts (5 activating, 3 loss-of-function), covering Invasive Breast Carcinoma, Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma, Colon Adenocarcinoma, Hepatocellular Carcinoma, Head and Neck Squamous Cell Carcinoma, Pancreatic Adenocarcinoma and others.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · SETDB1 (Histone-lysine N-methyltransferase SETDB1) 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 Breast cancer, Colorectal cancer, Hepatocellular carcinoma and 5 more.
- 1 · What it is
SETDB1 (Histone-lysine N-methyltransferase SETDB1) 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 Breast cancer, Colorectal cancer, Hepatocellular carcinoma and 5 more.
- 2 · What goes wrong in cancer
Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3).
- 3 · How drugs use it
No product in this corpus aims at SETDB1 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:10761 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q15047 (protein name, function text, keywords and locations (REST API)); IntOGen SETDB1 (driver in 8 cohorts (Act 5, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. Location: Nucleus; Cytoplasm; Chromosome (UniProt). Locus 1q21.3 (HGNC).
- Breast cancer: IntOGen driver in 1 cohort (BRCA)
- Colorectal cancer: IntOGen driver in 1 cohort (COAD)
- Hepatocellular carcinoma: IntOGen driver in 1 cohort (HCC)
- Head and neck squamous cell carcinoma: IntOGen driver in 1 cohort (HNSC)
- Pancreatic ductal adenocarcinoma: IntOGen driver in 1 cohort (PAAD)
- Mesothelioma: IntOGen driver in 1 cohort (PLMESO)
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 5 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 3 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:"SETDB1" OR ABSTRACT:"SETDB1" OR TITLE:"SET domain bifurcated histone lysine methyltransferase 1" OR ABSTRACT:"SET domain bifurcated histone lysine methyltransferase 1" OR TITLE:"Histone-lysine N-methyltransferase SETDB1" OR ABSTRACT:"Histone-lysine N-methyltransferase SETDB1" OR TITLE:"KG1T" OR ABSTRACT:"KG1T" OR TITLE:"KIAA0067" OR ABSTRACT:"KIAA0067" OR TITLE:"KMT1E" OR ABSTRACT:"KMT1E") 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 SETDB1, not a curated reading list.
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