SMARCA5
SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 5
Gene Information Card
| Symbol | SMARCA5 |
|---|---|
| Full Name | SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.21 |
| NCBI Gene ID | 8467 ncbi.nlm.nih.gov/gene/8467 |
| Ensembl ID | ENSG00000153147 |
| UniProt ID | O60264 |
| OMIM ID | 603375 |
| HGNC ID | 11101 |
| Aliases | SNF2H, WCRF135, hISWI, hSNF2H |
Description
SMARCA5 encodes a member of the SWI/SNF family of proteins, specifically the ISWI chromatin remodeling complex ATPase subunit SNF2H. This protein is a core catalytic component of several ATP-dependent chromatin remodeling complexes (e.g., ACF, CHRAC, NoRC, WICH, RSF) that regulate nucleosome spacing, DNA replication, transcription, and repair. SMARCA5 is ubiquitously expressed and essential for cell viability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorders | Disruption of SMARCA5 function alters chromatin dynamics required for neuronal gene expression and brain development. | ClinVar; PMID: 31036916 |
| Cancer (various) | Overexpression or amplification of SMARCA5 is observed in multiple cancers, promoting proliferation and metastasis through chromatin remodeling. | COSMIC; PMID: 25691885 |
| Intellectual disability | De novo missense variants in SMARCA5 are associated with autosomal dominant intellectual disability. | ClinVar; PMID: 31036916 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 33.8 | High |
| Brain (cerebellum) | 27.5 | High |
| Bone marrow | 25.1 | High |
| Lung | 20.3 | Medium |
| Liver | 15.2 | Medium |
| Pancreas | 12.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 30.5 | High expression |
| HeLa (cervical) | 28.1 | High expression |
| HEK293 (embryonic kidney) | 26.3 | High expression |
| HepG2 (liver) | 22.0 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2023G>A (p.Glu675Lys) | Missense | Rare | Alters ATPase domain, likely loss of function |
| c.2441C>T (p.Pro814Leu) | Missense | Rare | Associated with intellectual disability |
| Amplification | Copy number gain | Frequent in breast cancer | Increased SMARCA5 expression |
Mutation functional classification
Loss of Function (LOF)
Missense variants in the ATPase domain (e.g., p.Glu675Lys) impair chromatin remodeling activity.
Gain of Function (GOF)
Gene amplification leading to overexpression is observed in cancers, potentially driving proliferation.
Dominant Negative (DN)
Not well characterized; some missense variants may exert dominant-negative effects by disrupting complex assembly.
View complete mutation data：
Gene Ontology (GO)
| • ATP-dependent chromatin remodeling (GO:0043044) | • DNA replication (GO:0006260) |
| • Transcription by RNA polymerase II (GO:0006366) | • DNA repair (GO:0006281) |
| • Chromatin binding (GO:0003682) | • ATP binding (GO:0005524) |
| • Nucleosome binding (GO:0031491) |
Pathways
• Chromatin remodeling by ISWI complexes (Reactome: R-HSA-5250913)
• DNA replication initiation (Reactome: R-HSA-68962)
• Transcriptional regulation by SMARCA5 (WikiPathways: WP3996)
Protein Summary
SMARCA5 (SNF2H) is a 1052-amino acid ATPase that serves as the catalytic engine for multiple ISWI-type chromatin remodeling complexes. It uses ATP hydrolysis to slide nucleosomes along DNA, thereby regulating access to genomic DNA for replication, transcription, and repair. The protein contains a conserved SNF2_N domain, a helicase ATP-binding domain, and a HAND-SLIDE domain that mediates nucleosome interaction. SMARCA5 is essential for embryonic development and is implicated in neurodevelopmental disorders and cancer.
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