SMARCA2

Official Full Name

SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2

Organism

Homo sapiens

Gene ID

6595

Background

The protein encoded by this gene is a member of the SWI/SNF family of proteins and is highly similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, which contains a trinucleotide repeat (CAG) length polymorphism. [provided by RefSeq, Jan 2014]

Synonyms

BIS; BRM; SNF2; SWI2; hBRM; NCBRS; Sth1p; BAF190; SNF2L2; SNF2LA; hSNF2a

Cat.No.	Product Name	Price
CSC-DC014723	Panoply™ Human SMARCA2 Knockdown Stable Cell Line	Inquiry
CSC-SC014723	Panoply™ Human SMARCA2 Over-expressing Stable Cell Line	Inquiry
CSC-RT1565	Human SMARCA2 Knockout Cell Line-HeLa	Inquiry
CLKO-1412	SMARCA2 KO Cell Lysate-HeLa	Inquiry

Cat.No.	Product Name	Price
AD15132Z	Human SMARCA2 adenoviral particles	Inquiry
LV26082L	human SMARCA2 (NM_003070) lentivirus particles	Inquiry
LV26083L	human SMARCA2 (NM_139045) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH413088	shRNA set against Human SMARCA2 (NM_003070.3)	Inquiry
SHH413092	shRNA set against Mouse SMARCA2 (NM_011416.2)	Inquiry
SHH413096	shRNA set against Rat SMARCA2 (NM_001004446.1)	Inquiry
SHL015622	shRNA set against Human SMARCA2(NM_003070.3)	Inquiry
SHL015624	shRNA set against Rat Smarca2(NM_001004446.1)	Inquiry
SHL015642	shRNA set against Mouse Smarca2(NM_026003.2)	Inquiry
SHL015660	shRNA set against Human SMARCA2(NM_139045.2)	Inquiry
SHL015678	shRNA set against Human SMARCA2(NM_003070.3)	Inquiry
SHL015762	shRNA set against Mouse Smarca2(NM_011416.2)	Inquiry
SHW005639	shRNA set against Chicken SMARCA2 (NM_205139)	Inquiry
SHW009806	shRNA set against Danio rerio SMARCA2 (NM_001044775)	Inquiry
SHW015515	shRNA set against Danio rerio SMARCA4A (NM_181603)	Inquiry
SHW017876	shRNA set against Danio rerio SMARCA2 (NM_212716)	Inquiry

Cat.No.	Product Name	Price
MiUTR1R-07558	SMARCA2 miRNA 3'UTR clone	Inquiry
MiUTR1M-10979	SMARCA2 miRNA 3'UTR clone	Inquiry
MiUTR1H-09644	SMARCA2 miRNA 3'UTR clone	Inquiry
MiUTR1H-09643	SMARCA2 miRNA 3'UTR clone	Inquiry
CDFR001439	Rat Smarca2 cDNA Clone(NM_001004446.1)	Inquiry
CDFL012716	Mouse Smarca2 cDNA Clone(NM_011416.2)	Inquiry
CDFH018136	Human SMARCA2 cDNA Clone(NM_003070.3)	Inquiry
CDCH083400	Mouse Smarca2 ORF clone (NM_011416.2)	Inquiry
CDFG008368	Human SMARCA2 cDNA Clone(NM_139045.2)	Inquiry
MiUTR1M-10980	SMARCA2 miRNA 3'UTR clone	Inquiry
CDCR368360	Rat Smarca2 ORF Clone(NM_001004446.1)	Inquiry
CDCH083396	human SMARCA2 ORF clone (NM_139045.2)	Inquiry
CDCH083394	human SMARCA2 ORF clone (NM_003070.3)	Inquiry
CDCB194434	Rabbit SMARCA2 ORF clone (XM_002708185.2)	Inquiry
CDCB179351	Danio rerio SMARCA2 ORF Clone (NM_212716)	Inquiry
CDCB176990	Danio rerio SMARCA4A ORF Clone (NM_181603)	Inquiry
CDCB171281	Danio rerio SMARCA2 ORF Clone (NM_001044775)	Inquiry
CDCH083402	Mouse Smarca2 ORF clone (NM_026003.2)	Inquiry
CDCB167114	Chicken SMARCA2 ORF Clone (NM_205139)	Inquiry

Detailed Information

The SMARCA2 gene, also known as BRM, is located on human chromosome 9p24.3 and encodes one of the highly conserved catalytic subunits of the SWI/SNF chromatin remodeling complex. The encoded protein belongs to the SNF2-like helicase superfamily, featuring a central DExH domain with ATP hydrolysis activity and a C-terminal bromodomain. The bromodomain functions as a key "epigenetic reader," specifically recognizing and binding acetylated lysine residues on histone tails, a core mechanism for translating chromatin modification states into defined gene expression programs. SMARCA2, together with its closely related paralog SMARCA4, represents the two primary ATPase motors in mammalian cells, driving SWI/SNF-mediated chromatin remodeling activity. Notably, the SMARCA2 gene contains a polymorphic trinucleotide repeat, whose biological significance remains under investigation. Through complex alternative splicing, SMARCA2 can generate multiple protein isoforms with potentially subtle functional differences, further increasing its regulatory complexity and precision in gene networks.

Figure 1. Domain organization of SMARCA2, shown in a 3D model and a bar-like representation. (Guo Z, et al., 2025)

Biological Significance

SMARCA2's biological importance lies in its role as a central engine of chromatin remodeling. The SWI/SNF complex harnesses the energy from SMARCA2-mediated ATP hydrolysis to systematically alter DNA-histone contacts within nucleosomes, dynamically regulating chromatin structure and accessibility without changing the underlying DNA sequence. This remodeling activity can shift tightly packed, transcriptionally repressive chromatin into a relaxed, transcriptionally permissive state and vice versa, allowing SMARCA2 to function as either a transcriptional activator or repressor depending on context. This dual functionality is critical for maintaining cell identity, regulating the cell cycle, and determining cell fate.

During neural development, SMARCA2 plays a particularly nuanced role. It is incorporated into neural progenitor-specific (npBAF) and neuron-specific (nBAF) chromatin remodeling complexes. At key developmental transitions, as neural progenitor cells exit the cell cycle and differentiate into mature post-mitotic neurons, specific subunits in the npBAF complex are replaced by homologous subunits in the nBAF complex. SMARCA2 remains present throughout this transition, but its functional output depends on the complex context. The npBAF complex is essential for maintaining self-renewal and proliferative capacity in multipotent neural stem cells, whereas the nBAF complex collaborates with proteins such as CREST to activate gene programs critical for dendritic growth and neuronal morphology, thereby establishing the anatomical basis for neural network connectivity. Furthermore, loss or dysfunction of SMARCA2 expression is closely linked to uncontrolled cell proliferation, and its potential role as a tumor suppressor is increasingly recognized across multiple cancers.

Clinical Relevance

Clinically, SMARCA2 is relevant in cancer and neurodevelopmental disorders. In oncology, SMARCA2 is mutated or downregulated in several malignancies, including lung cancer, lymphoma, and hepatocellular carcinoma. Loss of function may promote tumorigenesis by impairing the activation of tumor suppressor genes mediated by chromatin remodeling. A more translationally promising discovery is the "addiction" of SMARCA4-deficient cancers to SMARCA2 function. SMARCA4, SMARCA2's closest paralog, is frequently mutated in many cancers. When SMARCA4 function is lost, SMARCA2 becomes the essential alternative ATPase for maintaining cell survival and proliferation. This synthetic lethality provides a precise therapeutic target, and the development of potent, selective SMARCA2 bromodomain inhibitors has become a focus in anticancer drug discovery. These small molecules competitively occupy the acetyl-lysine binding pocket of SMARCA2, disrupting its chromatin binding and remodeling functions, selectively inducing growth arrest and apoptosis in SMARCA4-deficient cancer cells while sparing cells with functional SMARCA4.

Beyond cancer, SMARCA2 dysfunction is also associated with certain neurodevelopmental disorders, although the mechanisms are less well defined. Given its critical role in neuronal differentiation and dendritic development, SMARCA2 single nucleotide polymorphisms or rare variants may contribute to individual susceptibility to neuropsychiatric conditions. Overall, as a hub connecting epigenetic regulation with core cellular functions, SMARCA2 represents a clinically valuable target, and synthetic lethality-based therapeutic strategies offer a promising avenue for precision oncology.

References

Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer. 2011;11(7):481-492.
Field NR, Dickson KA, Nassif NT, et al. SMARCA4 and SMARCA2 co-deficiency: An uncommon molecular signature defining a subset of rare, aggressive and undifferentiated malignancies associated with defective chromatin remodeling. Cancer Lett. 2024 Nov 28;605:217282.
Guo Z, Wang P, Han Y, et al. SMARCA2 protein: Structure, function and perspectives of drug design. Eur J Med Chem. 2025 Mar 15;286:117319.
Papillon JPN, Nakagawa N, Gajiwala KS, et al. Discovery of orally active inhibitors of Brahma homolog (BRM)/SMARCA2 ATPase activity for the treatment of Brahma related gene 1 (BRG1)/SMARCA4-mutant cancers. J Med Chem. 2018;61(22):10155-10172.

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