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Gene Symbol SMARCA4
Synonyms BAF190 | BAF190A | BRG1 | CSS4 | hSNF2b | MRD16 | OTSC12 | RTPS2 | SNF2 | SNF2-beta | SNF2L4 | SNF2LB | SWI2
Gene Description SMARCA4, SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4, is a member of the SWI/SNF family, which regulates transcription through chromatin remodeling (PMID: 27413115). Mutations in Smarca4 have been linked to rhabdoid tumors as well as breast, prostate, lung, pancreas, and colon cancers (PMID: 18437052, PMID: 24145903, PMID: 19234488).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
6597 19 19p13.2 NM_003072 Tumor suppressor (PMID: 30606230)

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
SMARCA4 loss lung non-small cell carcinoma sensitive Tozasertib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines with SMARCA4 loss demonstrated increased sensitivity to Tozasertib (VX-680), compared to cell lines expressing wild-type SMARCA4, in culture (Cancer Res July 15 2016 (76) (14 Supplement) LB-318). detail...
SMARCA4 loss Advanced Solid Tumor not applicable N/A Preclinical Emerging In a preclinical study, siRNA knockdown of BRM in SMARCA4-deficient tumor cells resulted in decreased growth and viability, suggesting that inhibition of BRM may be a promising therapeutic approach for targeting tumors with SMARCA4 loss (PMID: 23872584). 23872584
SMARCA4 loss lung cancer predicted - sensitive PRT7732 Preclinical Actionable In a preclinical study, PRT7732 inhibited tumor growth in a SMARCA4-deficient lung cancer xenograft model (Cancer Res (2024) 84 (6_Supplement): 4503). detail...
SMARCA4 loss Advanced Solid Tumor predicted - sensitive PRT7732 Preclinical - Cell culture Actionable In a preclinical study, PRT7732 inhibited proliferation of SMARCA4-deficient cancer cell lines in culture (Cancer Res (2024) 84 (6_Supplement): 4503). detail...
SMARCA4 mutant small-cell carcinoma of the ovary of hypercalcemic type sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Iclusig (ponatinib) treatment of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) cell lines and xenografts with mutant SMARCA4 resulted in decreased cell viability and tumor volume (PMID: 29440177). 29440177
SMARCA4 mutant lung non-small cell carcinoma predicted - sensitive Tozasertib Preclinical - Cell culture Actionable In a preclinical study, a non-small cell lung cancer cell line harboring a SMARCA4 mutation demonstrated sensitivity to Tozasertib (VX-680) in culture (Cancer Res July 15 2016 (76) (14 Supplement) LB-318). detail...
SMARCA4 mutant mantle cell lymphoma predicted - resistant Ibrutinib + Venetoclax Phase II Actionable In a Phase II trial (AIM), distinct molecular profiles were identified in mantle cell lymphoma patients responded to Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy compared to those did not respond, with all patients harboring mutations in NSD2 (n=4), UBR5 (n=3), KMT2D (n=3), and 12 of 13 patients harboring mutations in ATM responded to the therapy, while SMARCA4 (n=4), CCND1 (n=2), and NOTCH1 (n=3) alterations were exclusively observed in nonresponders (PMID: 30455436; NCT02471391). 30455436
SMARCA4 mutant lung non-small cell carcinoma predicted - sensitive PRT3789 Phase I Actionable In a Phase I trial, PRT3789 treatment was well tolerated and resulted in partial responses, tumor shrinkage, and prolonged stable disease in patients with advanced esophageal cancer (N=2) or non-small cell lung cancer (N=18) harboring SMARCA4 mutations (Ann Oncol (2024) 35 (suppl_2): S483-S484; NCT05639751). detail...
SMARCA4 mutant esophageal cancer predicted - sensitive PRT3789 Case Reports/Case Series Actionable In a Phase I trial, PRT3789 treatment was well tolerated and resulted in partial responses, tumor shrinkage, and prolonged stable disease in patients with advanced esophageal cancer (N=2) or non-small cell lung cancer (N=18) harboring SMARCA4 mutations (Ann Oncol (2024) 35 (suppl_2): S483-S484; NCT05639751). detail...
SMARCA4 mut TP53 mut adrenal gland cancer resistant Dabrafenib Preclinical Actionable In a preclinical study, human adrenal gland cancer cells harboring SMARCA4 and TP53 mutations were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 26343583). 26343583
SMARCA4 mut TP53 mut adrenal gland cancer resistant Vemurafenib Preclinical Actionable In a preclinical study, human adrenal gland cancer cells harboring SMARCA4 and TP53 mutations were resistant to Zelboraf (vemurafenib) mediated growth inhibition in culture (PMID: 26343583). 26343583
SMARCA4 mut TP53 mut adrenal gland cancer resistant LY3009120 Preclinical Actionable In a preclinical study, human adrenal gland cancer cells harboring SMARCA4 and TP53 mutations were resistant to LY3009120 mediated growth inhibition in culture (PMID: 26343583). 26343583
SMARCA4 inact mut lung non-small cell carcinoma sensitive Alisertib Preclinical - Cell culture Actionable In a preclinical study, a non-small cell lung cancer cell line harboring an inactivating mutation in SMARCA4 demonstrated sensitivity to Alisertib (MLN8237) in culture (PMID: 28102363). 28102363
SMARCA4 inact mut lung non-small cell carcinoma sensitive Danusertib Preclinical - Cell culture Actionable In a preclinical study, a non-small cell lung cancer cell line harboring an inactivating mutation in SMARCA4 demonstrated sensitivity to Danusertib (PHA-739358) in culture (PMID: 28102363). 28102363
SMARCA4 inact mut lung non-small cell carcinoma sensitive ENMD-2076 Preclinical - Cell culture Actionable In a preclinical study, a non-small cell lung cancer cell line harboring an inactivating mutation in SMARCA4 demonstrated sensitivity to ENMD-2076 in culture (PMID: 28102363). 28102363
SMARCA4 inact mut Advanced Solid Tumor no benefit Palbociclib Clinical Study Actionable In a combined analysis of 2 clinical trials (DRUP, MoST), Ibrance (palbociclib) or Kisqali (ribociclib) monotherapy had limited efficacy and resulted in no objective responses, a 15% clinical benefit rate at 16 weeks, median progression-free survival of 4 mo, and median overall survival of 5 mo in previously treated advanced solid tumor patients (n=112) with inactivating SMARCA4 mutations, CDKN2A loss, or CDK4, CDK6, CCND1, CCND2, or CCND3 amplification (PMID: 37424386; NCT02925234, ACTRN12616000931471). 37424386
SMARCA4 inact mut lung non-small cell carcinoma sensitive Tozasertib Preclinical - Cell line xenograft Actionable In a preclinical study, non-small cell lung cancer cell lines harboring SMARCA4 inactivating mutations demonstrated sensitivity to Tozasertib (VX-680) in culture and in xenograft models (PMID: 28102363). 28102363
SMARCA4 inact mut lung non-small cell carcinoma sensitive MK-5108 Preclinical - Cell culture Actionable In a preclinical study, a non-small cell lung cancer cell line harboring an inactivating mutation in SMARCA4 demonstrated sensitivity to MK-5108 (VX-689) in culture (PMID: 28102363). 28102363
SMARCA4 inact mut melanoma not predictive unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including SMARCA4, did not correlate with improved survival in 2 separate cohorts of patients with melanoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 1.70 (p=0.192, n=86) and 1.02 (p=0.939, n=192), respectively (PMID: 32321774). 32321774
SMARCA4 inact mut transitional cell carcinoma not predictive unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including SMARCA4, did not correlate with improved survival in 2 separate cohorts of patients with transitional cell carcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 1.44 (p=0.34, n=56) and 0.82 (p=0.559, n=93), respectively (PMID: 32321774). 32321774
SMARCA4 inact mut head and neck squamous cell carcinoma not predictive unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including SMARCA4, did not correlate with improved survival in 2 separate cohorts of patients with head and neck squamous cell carcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 0.74 (p=0.631, n=31) and 0.76 (p=0.622, n=68), respectively (PMID: 32321774). 32321774
SMARCA4 inact mut colorectal adenocarcinoma unknown unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including SMARCA4, correlated with improved survival in one cohort of patients with colorectal adenocarcinoma treated with systemic immune checkpoint inhibitors but not the other, with adjusted HRs for overall survival of 0.30 (p=0.03, n=35) and 0.56 (p=0.244, n=63), respectively (PMID: 32321774). 32321774
SMARCA4 inact mut gastroesophageal adenocarcinoma not predictive unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including SMARCA4, did not correlate with improved survival in 2 separate cohorts of patients with gastroesophageal adenocarcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 0.70 (p=0.403, n=66) and 0.46 (p=0.071, n=59), respectively (PMID: 32321774). 32321774
SMARCA4 negative rhabdoid cancer predicted - sensitive Tazemetostat Case Reports/Case Series Actionable In a Phase I trial, Tazemetostat (EPZ-6438) demonstrated safety and preliminary efficacy, resulted in 1 partial response and 1 durable stable disease in patient with SMARCA4-negative malignant rhabdoid tumor of the ovary (PMID: 29650362; NCT01897571). 29650362
SMARCA4 negative Advanced Solid Tumor predicted - sensitive Tazemetostat Phase I Actionable In a Phase I trial, Tazemetostat (EPZ-6438) demonstrated safety and preliminary efficacy, resulted in clinical benefit (stable disease or better) in 38% (5/13) of patients with SMARCB1 or SMARCA4-negative advanced solid tumors (PMID: 29650362; NCT01897571). 29650362
SMARCA4 del lung non-small cell carcinoma predicted - sensitive PRT3789 Preclinical - Pdx & cell culture Actionable In a preclinical study, PRT3789 inhibited proliferation of non-small cell lung cancer cells with deletion of SMARCA4 in culture and inhibited tumor growth in cell line xenograft and patient-derived xenograft (PDX) models (Cancer Res 2022;82(12_Suppl):Abstract nr 3263). detail...
SMARCA4 del melanoma sensitive SMD-3040 Preclinical - Cell line xenograft Actionable In a preclinical study, SMD-3040 inhibited proliferation of a melanoma cell line with SMARCA4 deletion in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 37523716). 37523716
SMARCA4 del lung non-small cell carcinoma sensitive SMD-3040 Preclinical - Cell line xenograft Actionable In a preclinical study, SMD-3040 inhibited proliferation of a non-small cell lung cancer cell line with SMARCA4 deletion in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 37523716). 37523716