SMARCA4 Gene: SWI/SNF-Related, Matrix-Associated, Actin-Dependent Regulator of Chromatin, Subfamily A, Member 4
A critical chromatin remodeler implicated in cancer and neurodevelopmental disorders
Gene Information Card
| Symbol | SMARCA4 |
|---|---|
| Full Name | SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 |
| Gene Type | protein coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 6597 ncbi.nlm.nih.gov/gene/6597 |
| Ensembl ID | ENSG00000127616 |
| UniProt ID | P51532 |
| OMIM ID | 603254 |
| HGNC ID | 11100 |
| Aliases | BRG1, BAF190, SNF2L4, SWI2, hSNF2b, MRD16, RTPS2 |
Description
SMARCA4 encodes BRG1, a catalytic subunit of the SWI/SNF chromatin remodeling complex. This ATPase uses energy from ATP hydrolysis to alter nucleosome structure, thereby regulating gene expression, DNA repair, and cell cycle control. SMARCA4 is a tumor suppressor frequently mutated in various cancers, and germline mutations cause neurodevelopmental disorders such as Coffin-Siris syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) | Biallelic inactivating mutations (loss of function) leading to loss of BRG1 protein expression | Somatic and germline mutations; loss of BRG1 expression by immunohistochemistry is a diagnostic marker (source: OMIM, COSMIC) |
| Malignant rhabdoid tumors (MRT) | Inactivating mutations or deletions causing loss of BRG1 function | Somatic mutations; SMARCA4 loss is a hallmark of extra-cranial rhabdoid tumors (source: COSMIC, ClinVar) |
| Coffin-Siris syndrome (CSS) | Heterozygous germline loss-of-function mutations (dominant negative or haploinsufficiency) | Pathogenic variants reported in ClinVar; OMIM #603254 |
| Non-small cell lung cancer (NSCLC) | Somatic inactivating mutations (frameshift, nonsense, splice site) leading to loss of tumor suppressor function | Recurrent mutations in lung adenocarcinoma and squamous cell carcinoma (source: COSMIC) |
| Colorectal cancer | Somatic mutations, often with microsatellite instability | COSMIC database; SMARCA4 mutations are frequent in MSI-high tumors |
| Neurodevelopmental delay/intellectual disability | Germline missense or truncating mutations affecting chromatin remodeling activity | ClinVar and OMIM entries for MRD16 (Mental retardation, autosomal dominant 16) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 20.1 | High |
| Brain (cerebellum) | 15.3 | Medium |
| Lung | 12.8 | Medium |
| Liver | 10.5 | Medium |
| Kidney | 9.7 | Low |
| Heart | 8.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 25.4 | High expression; used in SMARCA4 studies |
| HeLa (cervical adenocarcinoma) | 18.7 | Moderate expression |
| MCF7 (breast cancer) | 15.2 | Moderate expression |
| K562 (leukemia) | 12.3 | Low expression |
| HepG2 (hepatocellular carcinoma) | 10.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg1192Ter | Nonsense | ~2% in SCCOHT | Loss of function; truncates protein, leading to loss of ATPase domain |
| p.Glu861Lys | Missense | Rare in CSS | Dominant negative; affects ATPase activity |
| c.2034+1G>A | Splice site | ~1% in NSCLC | Loss of function; aberrant splicing, reduced protein |
| p.Leu1084Pro | Missense | Rare in CSS | Dominant negative; disrupts helicase domain |
| p.Arg974Trp | Missense | Rare in MRT | Loss of function; affects DNA binding |
Mutation functional classification
Loss of Function (LOF)
Most common in cancer (SCCOHT, MRT, NSCLC). Includes nonsense, frameshift, splice-site mutations leading to truncated or absent protein, resulting in loss of chromatin remodeling activity.
Gain of Function (GOF)
Rare; some missense mutations may confer oncogenic properties, but evidence is limited. Not well-documented in SMARCA4.
Dominant Negative (DN)
Observed in Coffin-Siris syndrome; missense mutations in the ATPase domain can interfere with the function of the wild-type allele, exerting a dominant-negative effect.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • DNA binding |
| • Helicase activity | • Chromatin binding |
| • Nucleosome remodeling | • Transcription regulation |
| • DNA repair | • Cell cycle |
Pathways
• SWI/SNF complex pathway
• Chromatin remodeling
• p53 signaling
• Cell cycle checkpoints
• DNA damage response
Protein Summary
BRG1 (SMARCA4) is a 1647-amino acid protein containing a helicase/ATPase domain and a bromodomain. It is the catalytic core of the SWI/SNF complex, which uses ATP to remodel nucleosomes, thereby regulating transcription. BRG1 interacts with various transcription factors and tumor suppressors, including RB1 and p53. Loss of BRG1 function is oncogenic, and its expression is a diagnostic marker in certain cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMARCA4 Knockout HEK293 Cell Line | EDJ-KQ15359 | Human | 6597 | Details Get a Quote |
| SMARCA4 Knockout HeLa Cell Line | EDJ-KQ18175 | Human | 6597 | Details Get a Quote |
| SMARCA4 Knockout HCT 116 Cell Line | EDJ-KQ46095 | Human | 6597 | Details Get a Quote |
| SMARCA4 Knockout A-549 Cell Line | EDJ-KQ44863 | Human | 6597 | Details Get a Quote |
| Smarca4 Knockout 4T1 Cell Line | EDJ-KZ48 | Mouse | 20586 | Details Get a Quote |
| SMARCA4 Knockout Hep-G2 Cell Line | EDJ-KZ480 | Human | 6597 | Details Get a Quote |
| Smarca4 Knockout ID8 Cell Line | EDJ-KZ481 | Mouse | 20586 | Details Get a Quote |
