protein
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4
aka SMARCA4
Gene
SMARCA4
Organism
Homo sapiens(9606)
Length
1647 aa
Mass
184,646 Da
SMARCA4 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4) is an ATP-dependent chromatin remodeling enzyme that alters DNA-histone interactions within nucleosomes to regulate transcriptional activation and repression (UniProt: P51532). It functions as a core component of SWI/SNF complexes and participates in the CREST-BRG1 complex, which orchestrates calcium-dependent gene activation in neurons by coordinating the removal of repressor complexes and recruitment of transcriptional activators.
SMARCA4 plays critical roles in neural development through its involvement in both neural progenitor-specific (npBAF) and neuron-specific (nBAF) chromatin remodeling complexes. During neural differentiation, SMARCA4-containing complexes switch subunit composition to support the transition from proliferating neural stem cells to postmitotic neurons, with roles in self-renewal, dendrite growth, and regulation of genes essential for neuronal function (UniProt: P51532). The protein is associated with several disorders including Coffin-Siris syndrome 4, a congenital malformation syndrome featuring intellectual disability and developmental delay, as well as rhabdoid tumor predisposition and otosclerosis.
SMARCA4 carries a SFARI syndromic classification (SFARI Cat S), reflecting an established association with autism spectrum disorder in the context of broader neurodevelopmental and genetic syndromes.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:15075294, PubMed:29374058, PubMed:30339381, PubMed:32459350). Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating the calcium-dependent release of a repressor complex and the recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by SMARCA4-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves the release of HDAC1 and recruitment of CREBBP (By similarity). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development, a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. SMARCA4/BAF190A may promote neural stem cell self-renewal/proliferation by enhancing Notch-dependent proliferative signals, while concurrently making the neural stem cell insensitive to SHH-dependent differentiating cues (By similarity). Acts as a corepressor of ZEB1 to regulate E-cadherin transcription and is required for induction of epithelial-mesenchymal transition (EMT) by ZEB1 (PubMed:20418909). Binds via DLX1 to enhancers located in the intergenic region between DLX5 and DLX6 and this binding is stabilized by the long non-coding RNA (lncRNA) Evf2 (By similarity). Binds to RNA in a promiscuous manner (By similarity). In brown adipose tissue, involved in the regulation of thermogenic genes expression (By similarity)
Disease associations
Rhabdoid tumor predisposition syndrome 2RTPS2
A familial cancer syndrome predisposing to renal or extrarenal malignant rhabdoid tumors and to a variety of tumors of the central nervous system, including choroid plexus carcinoma, medulloblastoma, and central primitive neuroectodermal tumors. Rhabdoid tumors are the most aggressive and lethal malignancies occurring in early childhood.
Coffin-Siris syndrome 4CSS4
A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported.
Otosclerosis 12OTSC12
A form of otosclerosis, a pathological condition of the ear characterized by formation of spongy bone in the labyrinth capsule, especially in front of and posterior to the footplate of the stapes, resulting in conductive hearing impairment. Cochlear otosclerosis may also develop, resulting in sensorineural hearing loss. OTSC12 is an autosomal dominant form with incomplete penetrance.
Sources
Last updated 5/6/2026, 5:24:27 AM