PRDM16
PRDM16 (Histone-lysine N-methyltransferase PRDM16) is a protein that switches other genes on and off. The public catalogues list it as a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma, Breast cancer, Neuroendocrine tumours and 4 more.
Overview
Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context. In the cytoplasm, acts as a histone methyltransferase, which catalyses monomethylation of 'Lys-9' of free histone H3 (H3K9me1) during translation. Monomethylated histone H3 is then transported to the nucleus and incorporated into nucleosomes where SUV39H methyltransferases (SUV39H1 and SUV39H2) use it as a substrate to catalyse histone H3 'Lys-9' trimethylation (H3K9me3).
Open Targets scores its association with cancer at 0.73 (direct and indirect evidence; datatypes literature 0.93, animal model 0.63, genetic association 0.55, somatic mutation 0.83). IntOGen calls it a driver in 1 cohort (0 activating, 0 loss-of-function), covering Plasma Cell Myeloma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PRDM16 (Histone-lysine N-methyltransferase PRDM16) is a protein that switches other genes on and off. The public catalogues list it as a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma, Breast cancer, Neuroendocrine tumours and 4 more.
- 1 · What it is
PRDM16 (Histone-lysine N-methyltransferase PRDM16) is a protein that switches other genes on and off. The public catalogues list it as a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma, Breast cancer, Neuroendocrine tumours and 4 more.
- 2 · What goes wrong in cancer
Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context.
- 3 · How drugs use it
No product in this corpus aims at PRDM16 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:14000 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9HAZ2 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000142611 (association with cancer (MONDO_0004992) 0.73; per-cancer scores at or above 0.5: melanoma 0.50, sarcoma 0.51, neuroendocrine neoplasm 0.55, skin cancer 0.55, breast cancer 0.56, lung cancer 0.53 (GraphQL API, CC0)); IntOGen PRDM16 (driver in 1 cohort (Act 0, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context. In the cytoplasm, acts as a histone methyltransferase, which catalyses monomethylation of 'Lys-9' of free histone H3 (H3K9me1) during translation. Monomethylated histone H3 is then transported to the nucleus and incorporated into nucleosomes where SUV39H methyltransferases (SUV39H1 and SUV39H2) use it as a substrate to catalyse histone H3 'Lys-9' trimethylation (H3K9me3). Probably one of the primary histone methyltransferases along with MECOM/PRDM3 that direct cytoplasmic H3K9me1 methylation. In the nucleus, acts as a key chromatin adapter that mediates differentiation of brown and beige adipocytes, which are specialised in dissipating chemical energy in the form of heat in response to cold or excess feeding. Following recruitment to chromatin by PPARG nuclear receptor, promotes differentiation of myoblastic precursors into brown adipose cells. Location: Nucleus; Chromosome; Cytoplasm (UniProt). Locus 1p36.32 (HGNC).
- Multiple myeloma: IntOGen driver in 1 cohort (PCM)
- Breast cancer: Open Targets association 0.56 with breast cancer (MONDO_0007254)
- Neuroendocrine tumours: Open Targets association 0.55 with neuroendocrine neoplasm (MONDO_0019496)
- Skin cancer: Open Targets association 0.55 with skin cancer (MONDO_0002898)
- Lung cancer: Open Targets association 0.53 with lung cancer (MONDO_0008903)
- Sarcomas: Open Targets association 0.51 with sarcoma (MONDO_0005089)
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: UniProt disease notes describe a translocation or gene fusion involving the gene. 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:"PRDM16" OR ABSTRACT:"PRDM16" OR TITLE:"PR/SET domain 16" OR ABSTRACT:"PR/SET domain 16" OR TITLE:"Histone-lysine N-methyltransferase PRDM16" OR ABSTRACT:"Histone-lysine N-methyltransferase PRDM16" OR TITLE:"MEL1" OR ABSTRACT:"MEL1" OR TITLE:"PFM13" OR ABSTRACT:"PFM13" OR TITLE:"KIAA1675" OR ABSTRACT:"KIAA1675") 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 PRDM16, not a curated reading list.
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