{"entity":{"id":"asxl1","kind":"target","name":"ASXL1","aka":["ASXL transcriptional regulator 1","Polycomb group protein ASXL1","KIAA0978"],"tldr":"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.","summary":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:18318","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18318"},{"label":"UniProt Q8IXJ9","url":"https://www.uniprot.org/uniprotkb/Q8IXJ9/entry"},{"label":"NCBI Gene 171023","url":"https://www.ncbi.nlm.nih.gov/gene/171023"},{"label":"Ensembl ENSG00000171456","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000171456"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["myeloproliferative-neoplasms","leukaemia","mds","non-hodgkin-lymphoma","urothelial","breast-cancer","rcc","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-haematopoiesis"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"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: 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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"ASXL1","role":["oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:18318","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18318","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q8IXJ9","url":"https://www.uniprot.org/uniprotkb/Q8IXJ9/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene ASXL1","url":"https://civicdb.org/features/68","note":"8 evidence items, 0 assertions, 2 variants; diseases: Acute Myeloid Leukaemia, Myelodysplastic Syndrome, Myelofibrosis (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000171456","url":"https://platform.opentargets.org/target/ENSG00000171456/associations","note":"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)"},{"label":"IntOGen ASXL1","url":"https://www.intogen.org/search?gene=ASXL1","note":"driver in 17 cohorts (Act 1, LoF 16); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA ASXL1: RNA low tissue specificity; no normal tissue stained high. Distribution: 7 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Myeloid neoplasms, Leukaemia, Lymphoma, Bladder & urothelial cancer, Breast cancer (all types), Renal cell carcinoma, Colorectal cancer); Open Targets associates it with 3 specific cancer types at or above 0.5 (myelodysplastic syndrome, acute myeloid leukemia, myeloid leukemia). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt Q8IXJ9","url":"https://www.uniprot.org/uniprotkb/Q8IXJ9/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene ASXL1","url":"https://civicdb.org/features/68","note":"8 evidence items, 0 assertions, 2 variants; diseases: Acute Myeloid Leukaemia, Myelodysplastic Syndrome, Myelofibrosis (GraphQL API, CC0)"},{"label":"IntOGen ASXL1","url":"https://www.intogen.org/search?gene=ASXL1","note":"driver in 17 cohorts (Act 1, LoF 16); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas ASXL1 tissue","url":"https://www.proteinatlas.org/ENSG00000171456-ASXL1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000171456 associations","url":"https://platform.opentargets.org/target/ENSG00000171456/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:18318","ensembl":"ENSG00000171456","uniprot":"Q8IXJ9","entrez":"171023","firstDescribed":1999,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Nagase et al, DNA Res, 1999, \"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/10231032/","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).","whereFound":["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)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/asxl1/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"mds","kind":"cancer","name":"Myelodysplastic syndromes / neoplasms (MDS)","route":"/cancers/mds/"},{"id":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"pathway":[{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"}]}}