DAXX
DAXX (Death domain-associated protein 6) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Neuroendocrine tumours, Adrenocortical carcinoma, Pancreatic ductal adenocarcinoma and 2 more.
Overview
Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively.
Open Targets scores its association with cancer at 0.74 (direct and indirect evidence; datatypes literature 0.94, affected pathway 0.61, genetic association 0.00, somatic mutation 0.91). IntOGen calls it a driver in 3 cohorts (0 activating, 3 loss-of-function), covering Adrenocortical Carcinoma, Pancreas, Pancreatic Neuroendocrine Tumour.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · DAXX (Death domain-associated protein 6) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Neuroendocrine tumours, Adrenocortical carcinoma, Pancreatic ductal adenocarcinoma and 2 more.
- 1 · What it is
DAXX (Death domain-associated protein 6) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Neuroendocrine tumours, Adrenocortical carcinoma, Pancreatic ductal adenocarcinoma and 2 more.
- 2 · What goes wrong in cancer
Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription.
- 3 · How drugs use it
No product in this corpus aims at DAXX yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:2681 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9UER7 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000204209 (association with cancer (MONDO_0004992) 0.74; per-cancer scores at or above 0.5: melanoma 0.55, neuroendocrine neoplasm 0.61, skin cancer 0.55 (GraphQL API, CC0)); IntOGen DAXX (driver in 3 cohorts (Act 0, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activation of PAX3 and ETS1 through direct protein-protein interactions. Modulates PAX5 activity; the function seems to involve CREBBP. Location: Cytoplasm; Nucleus, nucleoplasm; Nucleus, PML body; Nucleus, nucleolus (UniProt). Locus 6p21.32 (HGNC).
- Neuroendocrine tumours: Open Targets association 0.61 with neuroendocrine neoplasm (MONDO_0019496); IntOGen driver in 1 cohort (PANET)
- Adrenocortical carcinoma: IntOGen driver in 1 cohort (ACC)
- Pancreatic ductal adenocarcinoma: IntOGen driver in 1 cohort (PANCREAS)
- Skin cancer: Open Targets association 0.55 with skin cancer (MONDO_0002898)
- Melanoma: Open Targets association 0.55 with melanoma (MONDO_0005105)
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 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:"DAXX" OR ABSTRACT:"DAXX" OR TITLE:"death domain associated protein" OR ABSTRACT:"death domain associated protein" OR TITLE:"Death domain-associated protein 6" OR ABSTRACT:"Death domain-associated protein 6" OR TITLE:"DAP6" OR ABSTRACT:"DAP6") 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 DAXX, not a curated reading list.
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