Table of Contents

Overview

SMARCA4 is a member of the SWI/SNF family of proteins. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which can allow expression of genes repressed by chromatin. Overall, components of SWI/SNF have been identified as an emerging theme in germinal centre-derived B-cell lymphomas.1

Experimental Evidence

Driver mutations affecting this gene in DLBCL/FL/BL have been experimentally demonstrated to cause a reduction or loss of function (LOF).2

Relevance tier by entity

Entity Tier Description
BL 1 High-confidence BL gene
DLBCL 1 High-confidence DLBCL gene
FL 1 High-confidence FL gene
MCL 1 High-confidence MCL gene
PMBL 2 Role of SMARCA4 mutations in PMBL requires confirmation

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 27 0.0248 [0.0156,0.034]
DLBCL GAMBL with Reddy 2,088 60 0.0287 [0.0216,0.0359]
DLBCL BC 231 5 0.0216 [0.0029,0.0404]
DLBCL Dana-Farber 303 5 0.0165 [0.0022,0.0308]
DLBCL NCI 470 14 0.0298 [0.0144,0.0452]
DLBCL Reddy 999 33 0.0330 [0.022,0.0441]
DLBCL DLBCL_ICGC 85 3 0.0353 [0,0.0745]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 25 0.0389 [0.024,0.0539]
FL GAMBL with Crouch 1,189 64 0.0538 [0.041,0.0667]
FL BC 379 13 0.0343 [0.016,0.0526]
FL Kalmbach 164 9 0.0549 [0.02,0.0897]
FL Crouch 547 39 0.0713 [0.0497,0.0929]
FL FL_ICGC 99 3 0.0303 [0,0.0641]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 76 0.2245 [0.1791,0.2698]
BL GAMBL without ICGC/Zhou 320 58 0.1812 [0.139,0.2234]
BL GAMBL with Panea 410 95 0.2150 [0.176,0.2539]
BL BLGSP 219 39 0.1781 [0.1274,0.2288]
BL Zhou/ICGC 90 37 0.4111 [0.3095,0.5128]
BL Panea 101 19 0.1881 [0.1119,0.2643]

MCL

pathology Collection N mutated Incidence CI
MCL GAMBL 160 10 0.0620 [0.0247,0.0994]
MCL BC_MCL 103 6 0.0583 [0.013,0.1035]
MCL Barcelona 57 4 0.0702 [0.0039,0.1365]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 16.4107 5.8661 0.0000
FL 4.9909 0.0000 0.2962
DLBCL 1.5958 2.1520 0.4033

Visualizations

Protein

View coding variants in ProteinPaint hg19 or hg38

Genome

View all variants in GenomePaint hg19 or hg38

Expression

Structure with HotMAPS hotspots
Structure with HotMAPS hotspots

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2012-11-11 : Richter : BL 2013-01-01 : Zhang : DLBCL 2017-01-26 : Krysiak : FL 2020-09-17 : Nadeu : MCL

References

1.
Lunning MA, Green MR. Mutation of chromatin modifiers; an emerging hallmark of germinal center B-cell lymphomas. Blood Cancer J. 2015 Oct 16;5(10):e361. PMCID: PMC4635197
2.
Fernando TM, Piskol R, Bainer R, Sokol ES, Trabucco SE, Zhang Q, Trinh H, Maund S, Kschonsak M, Chaudhuri S, Modrusan Z, Januario T, Yauch RL. Functional characterization of SMARCA4 variants identified by targeted exome-sequencing of 131,668 cancer patients. Nat Commun. 2020 Nov 3;11(1):5551. PMCID: PMC7609548
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Deng Q, Lakra P, Gou P, Yang H, Meydan C, Teater M, Chin C, Zhang W, Dinh T, Hussein U, Li X, Rojas E, Liu W, Reville PK, Kizhakeyil A, Barisic D, Parsons S, Wilson A, Henderson J, Scull B, Gurumurthy C, Vega F, Chadburn A, Cuglievan B, El-Mallawany NK, Allen C, Mason C, Melnick A, Green MR. SMARCA4 is a haploinsufficient B cell lymphoma tumor suppressor that fine-tunes centrocyte cell fate decisions. Cancer Cell. 2024 Apr 8;42(4):605–622.e11. PMCID: PMC11003852
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Richter J, Schlesner M, Hoffmann S, Kreuz M, Leich E, Burkhardt B, Rosolowski M, Ammerpohl O, Wagener R, Bernhart SH, Lenze D, Szczepanowski M, Paulsen M, Lipinski S, Russell RB, Adam-Klages S, Apic G, Claviez A, Hasenclever D, Hovestadt V, Hornig N, Korbel JO, Kube D, Langenberger D, Lawerenz C, Lisfeld J, Meyer K, Picelli S, Pischimarov J, Radlwimmer B, Rausch T, Rohde M, Schilhabel M, Scholtysik R, Spang R, Trautmann H, Zenz T, Borkhardt A, Drexler HG, Möller P, MacLeod RAF, Pott C, Schreiber S, Trümper L, Loeffler M, Stadler PF, Lichter P, Eils R, Küppers R, Hummel M, Klapper W, Rosenstiel P, Rosenwald A, Brors B, Siebert R, ICGC MMML-Seq Project. Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing. Nat Genet. 2012 Dec;44(12):1316–1320.

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Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.

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