ARID1A

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ARID1A

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ARID1A</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ARID1A</td>
</tr>
<tr>
<td class="label">HGNC ID</td>
<td>11110</td>
</tr>
<tr>
<td class="label">Entrez ID</td>
<td>8289</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>ENSG00000117713</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>1p36.11</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein-coding</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>[ARID1A protein](/proteins/arid1a-protein)</td>
</tr>
<tr>
<td class="label">Key Domains</td>
<td>ARID, DUF3518, nuclear localization signal</td>
</tr>
<tr>
<td class="label">Function</td>
<td>BAF chromatin remodeling complex subunit</td>
</tr>
<tr>
<td class="label">Disease Associations</td>
<td>[Alzheimer's disease](/diseases/alzheimers-disease), Coffin-Siris syndrome, intellectual disability</td>
</tr>
<tr>
<td class="label">Variant</td>
<td>Type</td>
</tr>
<tr>
<td class="label">Numerous LoF variants</td>
<td>Truncating</td>
</tr>
<tr>
<td class="label">rs2228527</td>
<td>Synonymous</td>
</tr>
<tr>
<td class="label">Enhancer accessibility loss</td>
<td>Epigenetic</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/breast-cancer" style="color:#ef9a9a">Breast Can

...

ARID1A

ARID1A (AT-Rich Interaction Domain 1A)

</div>

Overview

ARID1A is a human gene. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

ARID1A (AT-Rich Interaction Domain 1A), also known as BAF250A or SMARCF1, encodes a core subunit of the BAF (BRG1/BRM-Associated Factor) [chromatin remodeling](/mechanisms/chromatin-remodeling-neurodegeneration) complex, a mammalian SWI/SNF complex.[@kadoch2015] ARID1A is the most frequently mutated chromatin regulator in human disease. In the nervous system, ARID1A is essential for neural progenitor proliferation, neuronal differentiation, and synaptic gene regulation. Haploinsufficient mutations cause Coffin-Siris syndrome, and emerging evidence connects ARID1A dysfunction to [Alzheimer's disease](/diseases/alzheimers-disease) through impaired [chromatin remodeling](/mechanisms/chromatin-remodeling) at synaptic and neuroprotective gene loci.

Gene Structure and Expression

The ARID1A gene spans approximately 86 kb on chromosome 1p36.11 and contains 20 exons encoding a 2285-amino acid protein. ARID1A is ubiquitously expressed, with high levels in brain tissue including the [hippocampus](/brain-regions/hippocampus), cerebral [cortex](/brain-regions/cortex), and cerebellum. Expression is particularly enriched during embryonic brain development in neural progenitor cells and persists in postmitotic [neurons](/entities/neurons) throughout life.

Single-cell transcriptomic studies reveal ARID1A expression across all major brain cell types, with the highest expression in excitatory neurons and oligodendrocyte precursor cells. In the aging brain, ARID1A expression declines in hippocampal neurons, correlating with age-related cognitive decline and increased vulnerability to [neurodegeneration](/diseases/alzheimers-disease).[@gjoneska2015]

Protein Function and Mechanism

ARID1A serves as a specificity subunit of the canonical BAF (cBAF) complex, one of three mammalian SWI/SNF complexes. The BAF complex uses ATP hydrolysis to remodel nucleosomes, making DNA accessible for transcription, replication, and repair. ARID1A contributes:

ARID domain: Binds AT-rich DNA sequences without strict sequence specificity, providing genomic targeting
DUF3518 domain: Mediates protein-protein interactions within the BAF complex
C-terminal region: Contains interaction surfaces for transcription factors and histone modifications

ARID1A-containing cBAF complexes are recruited to enhancers and promoters of actively transcribed genes, where they maintain nucleosome-free regions essential for transcription factor binding.[@mashtalir2018] In neurons, cBAF complexes containing ARID1A regulate:

Synaptic plasticity genes: Activity-dependent transcription of immediate early genes ([FOS](/genes/fos), [ARC](/genes/arc), [BDNF](/genes/bdnf))

Neuronal identity genes: Maintenance of postmitotic neuronal gene expression programs

DNA damage response: Recruitment of repair machinery to double-strand breaks through nucleosome remodeling

BAF Complex Composition

The cBAF complex containing ARID1A consists of approximately 15 subunits, including the catalytic ATPase ([SMARCA4/BRG1](/genes/smarca4) or [SMARCA2/BRM](/genes/smarca2)), [SMARCB1/SNF5](/genes/smarcb1), and SMARCC1/2. ARID1A and [ARID1B](/genes/arid1b) are mutually exclusive subunits — a given cBAF complex contains one or the other, creating functionally distinct subcomplexes with different genomic targets.[@kadoch2015][@mashtalir2018]

Role in Neurodegeneration

Alzheimer's Disease

Multiple lines of evidence link ARID1A to [Alzheimer's disease](/diseases/alzheimers-disease):

Chromatin accessibility changes: AD brain tissue shows widespread loss of chromatin accessibility at enhancers regulated by ARID1A-containing BAF complexes, particularly at synaptic gene loci in hippocampal neurons.[@nativio2018][@gjoneska2015]

Interaction with [tau](/proteins/tau): Pathological [tau](/proteins/tau) accumulation disrupts nuclear ARID1A-BAF complexes, sequestering ARID1A in cytoplasmic aggregates and reducing chromatin remodeling capacity. This creates a feed-forward loop where epigenetic dysregulation promotes further tau pathology.

[Amyloid-beta](/proteins/amyloid-beta) response: ARID1A-BAF complexes regulate the transcriptional response to amyloid-beta exposure, including induction of neuroprotective genes such as [NFE2L2/NRF2](/genes/NFE2L2) and antioxidant defense programs.[@gjoneska2015]

Synaptic gene silencing: Reduced ARID1A in aging neurons leads to aberrant Polycomb-mediated silencing of synaptic genes, contributing to synaptic loss — the strongest correlate of cognitive decline in AD.[@nativio2018][@nott2019]

Coffin-Siris Syndrome

Heterozygous loss-of-function variants in ARID1A cause Coffin-Siris syndrome type 2, a neurodevelopmental disorder characterized by:

Intellectual disability (mild to moderate)
Speech delay
Coarse facial features
Fifth finger/nail hypoplasia
Corpus callosum abnormalities

This establishes ARID1A as essential for normal brain development and highlights the dosage sensitivity of BAF complex function.[@tsurusaki2012]

Common Variants and Risk Alleles

Therapeutic Implications

BAF complex restoration: Strategies to stabilize or restore BAF complex function in aging neurons could counteract chromatin accessibility loss in AD.
Synthetic lethality: ARID1A loss creates dependency on ARID1B and other compensatory pathways, providing potential therapeutic leverage.
[HDAC](/entities/hdac-enzymes) inhibitors: [Histone deacetylase](/entities/histone-deacetylase) inhibitors partially compensate for BAF complex dysfunction by maintaining chromatin acetylation at target loci. Vorinostat and other [epigenetic therapies](/therapeutics/epigenetic-therapies-neurodegeneration) are under investigation.[@nativio2018][@gjoneska2015]
EZH2 inhibitors: Blocking PRC2-mediated silencing at BAF target genes may restore expression of neuroprotective programs.

External Links

[OMIM: 603024](https://omim.org/entry/603024)
[GeneCards: ARID1A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ARID1A)
[UniProt: O14497](https://www.uniprot.org/uniprot/O14497)

References

[Tsurusaki et al., Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome (2012) (2012)](https://doi.org/10.1038/ng.2229)

[Nativio et al., Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease (2018) (2018)](https://doi.org/10.1038/s41593-018-0101-9)

[Nott et al., Brain cell type-specific enhancer-promoter interactome maps and disease-risk association (2019) (2019)](https://doi.org/10.1126/science.aay0793)

[Unknown, Kadoch & Crabtree, Mammalian SWI/SNF chromatin remodeling complexes and cancer (2015) (2015)](https://doi.org/10.1016/j.tig.2015.09.009)

[Mashtalir et al., Modular organization and assembly of SWI/SNF family chromatin remodeling complexes (2018) (2018)](https://doi.org/10.1016/j.cell.2018.09.032)

[Lessard et al., An essential switch in subunit composition of a chromatin remodeling complex during neural development (2007) (2007)](https://doi.org/10.1016/j.neuron.2007.06.019)

[Sun et al., ARID1A has context-dependent oncogenic and tumor suppressor functions in liver cancer (2017) (2017)](https://doi.org/10.1016/j.ccell.2017.04.002)

[Wenderski et al., Loss of the neural-specific BAF subunit ACTL6B relieves repression of early response genes (2020) (2020)](https://doi.org/10.1016/j.celrep.2020.02.064)

[Unknown, Mandel & Bhatt, Chromatin remodeling complexes in neurodevelopmental disorders (2022) (2022)](https://doi.org/10.1002/wdev.456)

[Gjoneska et al., Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer's disease (2015) (2015)](https://doi.org/10.1038/nature14252)

Pathway Diagram

The following diagram shows the key molecular relationships involving ARID1A discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

Pathway Diagram

The following diagram shows the key molecular relationships involving ARID1A discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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ARID1A

ARID1A

ARID1A

Overview

Gene Structure and Expression

Protein Function and Mechanism

BAF Complex Composition

Role in Neurodegeneration

Alzheimer's Disease

Coffin-Siris Syndrome

Common Variants and Risk Alleles

Therapeutic Implications

See Also

External Links

References

Pathway Diagram

Pathway Diagram