ASXL1
ASXL1 (Polycomb group protein ASXL1) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Myeloproliferative neoplasms, Leukaemia, Myelodysplastic syndromes / neoplasms and 5 more.
Overview
Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG). Acts as a coactivator of RARA and RXRA through association with NCOA1. Acts as a corepressor for PPARG and suppresses its adipocyte differentiation-inducing activity.
CIViC holds 8 clinical evidence items and 0 assertions across 2 variants. Open Targets scores its association with cancer at 0.85 (direct and indirect evidence; datatypes literature 0.98, animal model 0.66, genetic association 0.85, somatic mutation 0.93). IntOGen calls it a driver in 17 cohorts (1 activating, 16 loss-of-function), covering Acute Myeloid Leukaemia, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Renal Clear Cell Carcinoma, Cholangiocarcinoma, Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma 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 · ASXL1 (Polycomb group protein ASXL1) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Myeloproliferative neoplasms, Leukaemia, Myelodysplastic syndromes / neoplasms and 5 more.
- 1 · What it is
ASXL1 (Polycomb group protein ASXL1) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Myeloproliferative neoplasms, Leukaemia, Myelodysplastic syndromes / neoplasms and 5 more.
- 2 · What goes wrong in cancer
Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG).
- 3 · How drugs use it
No product in this corpus aims at ASXL1 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:18318 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q8IXJ9 (protein name, function text, keywords and locations (REST API)); CIViC gene ASXL1 (8 evidence items, 0 assertions, 2 variants; diseases: Acute Myeloid Leukaemia, Myelodysplastic Syndrome, Myelofibrosis (GraphQL API, CC0)); Open Targets ENSG00000171456 (association with cancer (MONDO_0004992) 0.85; per-cancer scores at or above 0.5: acute myeloid leukaemia 0.77, non-Hodgkin lymphoma 0.62, skin cancer 0.57, myelodysplastic syndrome 0.76, myeloproliferative neoplasm 0.83, leukaemia 0.83 (GraphQL API, CC0)); IntOGen ASXL1 (driver in 17 cohorts (Act 1, LoF 16); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG). Acts as a coactivator of RARA and RXRA through association with NCOA1. Acts as a corepressor for PPARG and suppresses its adipocyte differentiation-inducing activity. Non-catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1). Acts as a sensor of N(6)-methyladenine methylation on DNA (6mA): recognises and binds 6mA DNA, leading to its ubiquitination and degradation by TRIP12, thereby inactivating the PR-DUB complex and regulating Polycomb silencing. The PR-DUB complex is an epigenetic regulator of gene expression and acts as a transcriptional coactivator, affecting genes involved in development, cell communication, signalling, cell proliferation and cell viability. Location: Nucleus (UniProt). Locus 20q11.21 (HGNC).
- Myeloproliferative neoplasms: Open Targets association 0.83 with myeloproliferative neoplasm (MONDO_0020076)
- Leukaemia: Open Targets association 0.83 with leukaemia (MONDO_0005059)
- Myelodysplastic syndromes / neoplasms: Open Targets association 0.76 with myelodysplastic syndrome (MONDO_0018881); CIViC evidence names this disease
- Non-Hodgkin lymphoma: Open Targets association 0.62 with non-Hodgkin lymphoma (MONDO_0018908)
- Bladder & urothelial cancer: IntOGen driver in 1 cohort (BLCA)
- Breast cancer: IntOGen driver in 1 cohort (BRCA)
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 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 16 cohorts; CIViC holds 8 clinical evidence items on its variants. Evidence tier "clinical-evidence" 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: Myelofibrosis; High-Grade Glioma, NOS.
Latest papers
topQuery for this target: (TITLE:"ASXL1" OR ABSTRACT:"ASXL1" OR TITLE:"ASXL transcriptional regulator 1" OR ABSTRACT:"ASXL transcriptional regulator 1" OR TITLE:"Polycomb group protein ASXL1" OR ABSTRACT:"Polycomb group protein ASXL1" OR TITLE:"KIAA0978" OR ABSTRACT:"KIAA0978") 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 ASXL1, not a curated reading list.
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