SMARCA4
SMARCA4 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.
Overview
ATPase 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. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating the calcium-dependent release of a repressor complex and the recruitment of an activator complex.
CIViC holds 18 clinical evidence items and 0 assertions across 6 variants, naming Abemaciclib, Tazemetostat, Palbociclib and Vinorelbine and others. Open Targets scores its association with cancer at 0.90 (direct and indirect evidence; datatypes genetic literature 0.90, affected pathway 0.76, literature 1.00, genetic association 0.91, somatic mutation 0.98, animal model 0.56). IntOGen calls it a driver in 45 cohorts (27 activating, 16 loss-of-function), covering Burkitt Lymphoma, Bladder/Urinary Tract, Bladder Urothelial Carcinoma, Renal Clear Cell Carcinoma, Cholangiocarcinoma, Colon Adenocarcinoma 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 · SMARCA4 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.
- 1 · What it is
SMARCA4 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.
- 2 · What goes wrong in cancer
ATPase 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 SMARCA4 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:11100 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P51532 (protein name, function text, keywords and locations (REST API)); CIViC gene SMARCA4 (18 evidence items, 0 assertions, 6 variants; diseases: Lung Non-small Cell Carcinoma, Small-cell Carcinoma Of The Ovary Of Hypercalcemic Type, Small Cell Carcinoma Of The Ovary, Hypercalcaemic Type, Cancer, Lung Adenocarcinoma and 4 more (GraphQL API, CC0)); Open Targets ENSG00000127616 (association with cancer (MONDO_0004992) 0.90; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.69, colorectal cancer 0.57, gastric cancer 0.55, oesophageal cancer 0.56, ovarian cancer 0.65, melanoma 0.59 (GraphQL API, CC0)); IntOGen SMARCA4 (driver in 45 cohorts (Act 27, LoF 16); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
ATPase 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. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating the calcium-dependent release of a repressor complex and the recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by SMARCA4-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. Location: Nucleus (UniProt). Locus 19p13.2 (HGNC).
- Sarcomas: Open Targets association 0.84 with sarcoma (MONDO_0005089)
- Lung cancer: Open Targets association 0.70 with lung cancer (MONDO_0008903)
- Neuroendocrine tumours: Open Targets association 0.65 with neuroendocrine neoplasm (MONDO_0019496)
- Ovarian cancer: Open Targets association 0.65 with ovarian cancer (MONDO_0008170); IntOGen driver in 1 cohort (OVT)
- Oesophageal cancer: Open Targets association 0.56 with oesophageal cancer (MONDO_0007576); IntOGen driver in 6 cohorts (ESCA, ESCC)
- Pancreatic ductal adenocarcinoma: IntOGen driver in 5 cohorts (PAAD, PANCREAS)
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 7 therapies; IntOGen calls it an activating (Act) driver in 27 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 16 cohorts; CIViC holds 18 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: Small-cell Carcinoma Of The Ovary Of Hypercalcemic Type; Small Cell Carcinoma Of The Ovary, Hypercalcaemic Type; Ovarian Small Cell Carcinoma; Low-Grade Glioma, NOS.
Latest papers
topQuery for this target: (TITLE:"SMARCA4" OR ABSTRACT:"SMARCA4" OR TITLE:"SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4" OR ABSTRACT:"SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4" OR TITLE:"SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4" OR ABSTRACT:"SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4" OR TITLE:"hSNF2b" OR ABSTRACT:"hSNF2b" OR TITLE:"BRG1" OR ABSTRACT:"BRG1" OR TITLE:"BAF190" OR ABSTRACT:"BAF190") 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 SMARCA4, not a curated reading list.
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