ARID1A
ARID1A (AT-rich interactive domain-containing protein 1A) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Bladder & urothelial cancer, Colorectal cancer, Endometrial cancer and 5 more.
Overview
Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically.
CIViC holds 14 clinical evidence items and 0 assertions across 7 variants, naming Dasatinib, Sorafenib, Nivolumab and Pembrolizumab and others. Open Targets scores its association with cancer at 0.85 (direct and indirect evidence; datatypes literature 1.00, affected pathway 0.89, genetic association 0.57, somatic mutation 0.98). IntOGen calls it a driver in 90 cohorts (1 activating, 89 loss-of-function), covering Burkitt Lymphoma, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Renal Clear Cell Carcinoma, Cervical Squamous Cell Carcinoma, Cholangiocarcinoma 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 · ARID1A (AT-rich interactive domain-containing protein 1A) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Bladder & urothelial cancer, Colorectal cancer, Endometrial cancer and 5 more.
- 1 · What it is
ARID1A (AT-rich interactive domain-containing protein 1A) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Bladder & urothelial cancer, Colorectal cancer, Endometrial cancer and 5 more.
- 2 · What goes wrong in cancer
Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
- 3 · How drugs use it
No product in this corpus aims at ARID1A 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:11110 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O14497 (protein name, function text, keywords and locations (REST API)); CIViC gene ARID1A (14 evidence items, 0 assertions, 7 variants; diseases: Ovarian Clear Cell Carcinoma, Colorectal Cancer, Ovarian Cancer, Stomach Cancer, Diffuse Large B-cell Lymphoma and 4 more (GraphQL API, CC0)); Open Targets ENSG00000117713 (association with cancer (MONDO_0004992) 0.85; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.65, colorectal cancer 0.74, gastric cancer 0.69, oesophageal cancer 0.62, hepatocellular carcinoma 0.67, cholangiocarcinoma 0.53 (GraphQL API, CC0)); IntOGen ARID1A (driver in 90 cohorts (Act 1, LoF 89); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. Location: Nucleus (UniProt). Locus 1p36.11 (HGNC).
- Bladder & urothelial cancer: Open Targets association 0.76 with urinary bladder cancer (MONDO_0001187); IntOGen driver in 9 cohorts (BLCA, UTUC)
- Colorectal cancer: Open Targets association 0.74 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease
- Endometrial cancer: Open Targets association 0.72 with endometrial cancer (MONDO_0011962); IntOGen driver in 4 cohorts (UCEC)
- Gastric & gastro-oesophageal junction cancer: Open Targets association 0.69 with gastric cancer (MONDO_0001056); CIViC evidence names this disease
- Breast cancer: Open Targets association 0.68 with breast cancer (MONDO_0007254); IntOGen driver in 8 cohorts (BRCA)
- Lung cancer: Open Targets association 0.68 with lung cancer (MONDO_0008903); IntOGen driver in 1 cohort (LUNG)
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: CIViC lists 6 therapies; IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 89 cohorts; CIViC holds 14 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: Ovarian Clear Cell Carcinoma; Ovarian Clear Cell Adenocarcinoma; Low-Grade Glioma, NOS.
Latest papers
topQuery for this target: (TITLE:"ARID1A" OR ABSTRACT:"ARID1A" OR TITLE:"AT-rich interaction domain 1A" OR ABSTRACT:"AT-rich interaction domain 1A" OR TITLE:"AT-rich interactive domain-containing protein 1A" OR ABSTRACT:"AT-rich interactive domain-containing protein 1A" OR TITLE:"B120" OR ABSTRACT:"B120" OR TITLE:"P270" OR ABSTRACT:"P270" OR TITLE:"C10rf4" OR ABSTRACT:"C10rf4") 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 ARID1A, not a curated reading list.
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