ARID1B

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ARID1B

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ARID1B</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ARID1B</td>
</tr>
<tr>
<td class="label">HGNC ID</td>
<td>18040</td>
</tr>
<tr>
<td class="label">Entrez ID</td>
<td>57492</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>ENSG00000049618</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>6q25.3</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein-coding</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>[ARID1B protein](/proteins/arid1b-protein)</td>
</tr>
<tr>
<td class="label">Key Domains</td>
<td>ARID, DUF3518, C-terminal EHD</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 type 1, intellectual disability</td>
</tr>
<tr>
<td class="label">Variant</td>
<td>Type</td>
</tr>
<tr>
<td class="label">>150 LoF variants</td>
<td>Truncating/frameshift</td>
</tr>
<tr>
<td class="label">De novo LoF variants</td>
<td>Various</td>
</tr>
<tr>
<td class="label">Common enhancer variants</td>
<td>Regulatory</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

...

ARID1B

ARID1B (AT-Rich Interaction Domain 1B)

</div>

Overview

Mermaid diagram (expand to render)

ARID1B is a human gene. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

ARID1B (AT-Rich Interaction Domain 1B), also known as BAF250B, encodes a subunit of the BAF (BRG1/BRM-Associated Factor) [chromatin remodeling](/mechanisms/chromatin-remodeling-neurodegeneration) complex. ARID1B is mutually exclusive with [ARID1A](/genes/arid1a) in the canonical BAF (cBAF) complex, generating functionally distinct subcomplexes. ARID1B is the most commonly mutated gene in Coffin-Siris syndrome and among the most frequently mutated genes in intellectual disability. In the aging brain, ARID1B-containing BAF complexes play specialized roles in neuronal maintenance and neuroprotection, with implications for [Alzheimer's disease](/diseases/alzheimers-disease) and age-related cognitive decline.[@hoyer2012]

Gene Structure and Expression

The ARID1B gene spans approximately 475 kb on chromosome 6q25.3 and contains 20 exons encoding a 2236-amino acid protein. ARID1B shows a more restricted expression pattern than [ARID1A](/genes/arid1a), with particularly high expression in the developing and adult brain. During cortical development, ARID1B expression peaks during neurogenesis and is maintained at lower levels in mature [neurons](/entities/neurons).

In the adult human brain, ARID1B is expressed across all regions, with the highest levels in the [hippocampus](/brain-regions/hippocampus), amygdala, and cortical association areas. Single-cell transcriptomics reveal predominant expression in excitatory and inhibitory neurons, with lower levels in glial cells. Notably, ARID1B expression is relatively preserved in the aging brain compared to [ARID1A](/genes/arid1a), suggesting a compensatory role in maintaining chromatin accessibility during aging.

Protein Function and Mechanism

ARID1B serves as an alternative specificity subunit of the canonical BAF (cBAF) complex, defining a distinct subcomplex (ARID1B-cBAF) with different genomic targeting compared to ARID1A-cBAF. Key functional features include:

ARID domain: Binds AT-rich DNA with broader sequence recognition than ARID1A
DUF3518 domain: Mediates interactions with other BAF subunits
C-terminal EHD domain: Contributes to protein stability and interaction specificity

ARID1B-cBAF complexes preferentially target:

Neuronal enhancers: ARID1B-containing complexes are enriched at brain-specific enhancers controlling neuronal identity genes[@jung2019]

Activity-regulated genes: Response to neuronal activity drives ARID1B redistribution to immediate early gene enhancers[@wenderski2020]

Developmental genes: Maintenance of neural progenitor gene programs during differentiation

The ARID1A/ARID1B switch during development represents a critical transition: neural progenitors express both paralogs, while postmitotic neurons increasingly rely on ARID1B-cBAF for maintaining neuronal gene expression programs.[@lessard2007][@mashtalir2018]

Role in Neurodegeneration

Alzheimer's Disease

ARID1B is implicated in AD through several mechanisms:

Compensatory chromatin remodeling: As [ARID1A](/genes/arid1a) expression declines in aging neurons, ARID1B-cBAF becomes the primary chromatin remodeling complex at synaptic gene loci. When this compensation fails, widespread enhancer decommissioning occurs at neuroprotective genes.[@hoyer2012]

[Tau](/proteins/tau) interaction: ARID1B directly interacts with [tau protein](/proteins/tau), and this interaction is disrupted by pathological tau phosphorylation. Hyperphosphorylated tau sequesters ARID1B from the BAF complex, reducing chromatin remodeling at tau-regulated gene targets.[@hoyer2012]

Inflammatory gene regulation: ARID1B-cBAF complexes regulate the microglial transcriptional response to [amyloid-beta](/proteins/amyloid-beta), modulating expression of [TREM2](/genes/TREM2), [CX3CR1](/genes/CX3CR1), and complement genes. Loss of ARID1B function shifts [microglia](/cell-types/microglia-neuroinflammation) toward a neurotoxic activation state.[@hoyer2012]

Neuronal survival: ARID1B maintains expression of anti-apoptotic genes in mature neurons. Reduced ARID1B activity leads to downregulation of BCL2-family members and increased vulnerability to excitotoxicity and oxidative stress.[@ka2016]

Coffin-Siris Syndrome

Heterozygous loss-of-function variants in ARID1B are the most common cause of Coffin-Siris syndrome (type 1), accounting for approximately 68% of genetically confirmed cases. Features include:

Intellectual disability (moderate to severe)
Absent or hypoplastic fifth fingernails/toenails
Coarse facial features
Sparse scalp hair
Feeding difficulties
Agenesis or hypoplasia of the corpus callosum

ARID1B haploinsufficiency is also among the most common monogenic causes of intellectual disability overall, with many cases lacking the full Coffin-Siris phenotype.[@santen2012][@hoyer2012]

Common Variants and Risk Alleles

Therapeutic Implications

BAF complex stabilization: Pharmacological stabilization of residual ARID1B-BAF complexes could enhance chromatin remodeling in haploinsufficient neurons.
Compensatory targeting: Enhancing ARID1A expression to compensate for ARID1B loss (and vice versa) offers a paralog-based therapeutic strategy.
[HDAC](/entities/hdac-enzymes) inhibitors: [Epigenetic therapies](/therapeutics/epigenetic-therapies-neurodegeneration) using HDAC inhibitors can partially restore chromatin accessibility at BAF target genes.
Gene therapy: ASO-mediated upregulation of the remaining ARID1B allele through targeting of upstream regulatory elements is under preclinical investigation.[@wenderski2020]

External Links

[OMIM: 614556](https://omim.org/entry/614556)
[GeneCards: ARID1B](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ARID1B)
[UniProt: Q8NFD5](https://www.uniprot.org/uniprot/Q8NFD5)

References

[Santen et al., Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome (2012) (2012)](https://doi.org/10.1038/ng.2217)

[Hoyer et al., Haploinsufficiency of ARID1B is a frequent cause of intellectual disability (2012) (2012)](https://doi.org/10.1016/j.ajhg.2012.10.016)

[Savage et al., Genome-wide association meta-analysis of intelligence in over 269,867 individuals (2018) (2018)](https://doi.org/10.1038/s41588-018-0152-6)

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

[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)

[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)

[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)

[Vasileiou et al., Mutations in the BAF complex subunit DPF2 are associated with Coffin-Siris syndrome (2018) (2018)](https://doi.org/10.1016/j.ajhg.2018.01.014)

[Jung et al., BAF subunit switching regulates chromatin accessibility to control cell cycle exit in the developing mammalian cortex (2019) (2019)](https://doi.org/10.1101/gad.328559.119)

[Ka et al., ARID1B haploinsufficiency impairs cortical interneuron development (2016) (2016)](https://doi.org/10.1093/cercor/bhw218)

Pathway Diagram

The following diagram shows the key molecular relationships involving ARID1B discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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ARID1B

ARID1B

ARID1B

Overview

Gene Structure and Expression

Protein Function and Mechanism

Role in Neurodegeneration

Alzheimer's Disease

Coffin-Siris Syndrome

Common Variants and Risk Alleles

Therapeutic Implications

See Also

External Links

References

Pathway Diagram