{"entity":{"id":"smarca4","kind":"target","name":"SMARCA4","aka":["SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4","SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4","hSNF2b","BRG1","BAF190","SNF2","SWI2","SNF2-BETA","SNF2LB","FLJ39786","SNF2L4"],"tldr":"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.","summary":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:11100","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11100"},{"label":"UniProt P51532","url":"https://www.uniprot.org/uniprotkb/P51532/entry"},{"label":"NCBI Gene 6597","url":"https://www.ncbi.nlm.nih.gov/gene/6597"},{"label":"Ensembl ENSG00000127616","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000127616"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["sarcoma","lung-cancer","neuroendocrine","ovarian","esophageal","pancreatic","non-hodgkin-lymphoma","urothelial","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["swi-snf-chromatin"],"terms":[],"trials":["nct03213665"],"people":[],"bottlenecks":[],"keyPapers":["paper-schoenfeld-smarca4-alterations-lung-ccr-2020"],"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: 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.","Lung cancer: altered in 8% of 4,813 patients, in two classes that behave differently. Class 1 alterations (truncating, fusion, homozygous deletion) lose protein expression in 81% of cases and carry the shortest survival; class 2 missense alterations lose none. Both co-occur with KRAS, STK11 and KEAP1, and both did better than wild-type tumours on checkpoint blockade, class 1 best (Schoenfeld 2020). It reaches 11.2% in immunotherapy-treated cohorts and only 3.5% in squamous disease (cBioPortal)."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"SMARCA4","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:11100","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11100","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P51532","url":"https://www.uniprot.org/uniprotkb/P51532/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SMARCA4","url":"https://civicdb.org/features/78","note":"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)"},{"label":"Open Targets ENSG00000127616","url":"https://platform.opentargets.org/target/ENSG00000127616/associations","note":"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)"},{"label":"IntOGen SMARCA4","url":"https://www.intogen.org/search?gene=SMARCA4","note":"driver in 45 cohorts (Act 27, 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 SMARCA4: RNA low tissue specificity; high antibody staining in 37 normal tissues; highest cancer staining lung cancer (12 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Sarcomas (soft tissue, bone, GIST), Lung cancer (all types), Neuroendocrine tumours, Ovarian cancer, Oesophageal cancer, Pancreatic ductal adenocarcinoma, Lymphoma and more); Open Targets associates it with 9 specific cancer types at or above 0.5 (rhabdoid tumor predisposition syndrome 2, familial rhabdoid tumor, rhabdoid tumor, medulloblastoma, hereditary neoplastic syndrome, lung adenocarcinoma and more). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P51532","url":"https://www.uniprot.org/uniprotkb/P51532/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SMARCA4","url":"https://civicdb.org/features/78","note":"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)"},{"label":"IntOGen SMARCA4","url":"https://www.intogen.org/search?gene=SMARCA4","note":"driver in 45 cohorts (Act 27, LoF 16); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas SMARCA4 tissue","url":"https://www.proteinatlas.org/ENSG00000127616-SMARCA4/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000127616 associations","url":"https://platform.opentargets.org/target/ENSG00000127616/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11100","ensembl":"ENSG00000127616","uniprot":"P51532","entrez":"6597","firstDescribed":1993,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Khavari P.A. et al, Nature, 1993, \"BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8232556/","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).","whereFound":["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)","Non-small-cell lung cancer: truncating and missense mutation (class 1 and class 2) 6-10%"],"targetClass":"transcription","prevalence":[{"cancerId":"nsclc","pct":"6-10","measure":"Truncating and missense mutation (class 1 and class 2)","source":"https://www.cbioportal.org/study/summary?id=luad_mskcc_2023_met_organotropism","note":"cBioPortal: 228 of 2,653, 8.6%, in luad_mskcc_2023_met_organotropism; 92 of 915, 10.1%, in lung_msk_2017; 46 of 566, 8.1%, in luad_tcga_pan_can_atlas_2018; 11 of 110, 10.0%, in luad_cptac_2020; 27 of 240, 11.2%, in nsclc_pd1_msk_2018; 17 of 484, 3.5%, in lusc_tcga_pan_can_atlas_2018; 8 of 302, 2.6%, in luad_oncosg_2020. In 4,813 patients, 407, 8%, carried a SMARCA4 alteration (Schoenfeld 2020)."}]},"route":"/targets/smarca4/","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":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"pathway":[{"id":"swi-snf-chromatin","kind":"pathway","name":"SWI/SNF chromatin remodelling","route":"/pathways/swi-snf-chromatin/"}],"trial":[{"id":"nct03213665","kind":"trial","name":"Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)","route":"/trials/nct03213665/"}],"paper":[{"id":"paper-schoenfeld-smarca4-alterations-lung-ccr-2020","kind":"paper","name":"The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer","route":"/key-papers/paper-schoenfeld-smarca4-alterations-lung-ccr-2020/"}]}}