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ARID2
AT-rich interaction domain 2
ARID2 encodes a component of chromatin-remodelling complexes that regulate gene expression during brain development. The ARID2 gene provides instructions for making a protein that helps control which genes are switched on or off in cells.
ARID2 is located on the long (q) arm of chromosome 12, at band 12q12. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 12 in the library →Overview
ARID2 (AT-rich interaction domain 2) is located on chromosome 12 and encodes a 1,835 amino acid protein involved in chromatin remodelling. Chromatin refers to the complex of DNA and proteins that packages genetic material within the nucleus, and remodelling this structure is fundamental to controlling gene activity. The ARID2 protein acts as a subunit of the PBAF chromatin-remodelling complex, which repositions nucleosomes-the protein spools around which DNA winds-to make genes more or less accessible for transcription. Pathogenic variants in ARID2 follow an autosomal dominant inheritance pattern, meaning a single altered copy can disrupt normal development. These variants are recognised within the UK National Health Service genomic medicine framework for their association with neurodevelopmental presentations.
What the gene does
The ARID2 protein participates in the polybromo-associated BAF (PBAF) complex, a multi-subunit assembly that uses energy from ATP hydrolysis to slide, eject, or restructure nucleosomes along chromosomal DNA. By altering chromatin accessibility, the PBAF complex influences which genes are available for transcription at different developmental stages and in different cell types. ARID2 contributes to the DNA-binding specificity of the complex through its ARID domain, which recognises AT-rich sequences in the genome, and its RFX-type winged-helix domain, which facilitates additional interactions with DNA. Research suggests that proper PBAF function is particularly important during embryonic brain development, where precise temporal and spatial control of gene expression guides the formation of neural circuits. The protein also contains a C2H2-type zinc finger motif near its C-terminus, which may mediate interactions with other regulatory proteins. Loss of functional ARID2 is thought to impair the ability of developing neurons to execute correct gene-expression programmes, contributing to cognitive and developmental phenotypes.
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Chromosome location
ARID2 is situated on the long arm of chromosome 12 at cytogenetic band 12q12. The gene spans a substantial genomic region and produces a transcript encoding the full-length 1,835 amino acid protein. The chromosomal position places ARID2 within a region that harbours several other genes involved in developmental processes.
Protein structure
The ARID2 protein is organised into several functional domains and regions. Near the N-terminus, the ARID domain (amino acids 13-105) mediates binding to AT-rich DNA sequences, a hallmark of chromatin-remodelling proteins in this family. An LXXLL motif (amino acids 313-317) is present, which typically facilitates interactions with nuclear hormone receptors or other transcriptional regulators. The RFX-type winged-helix domain (amino acids 524-603) provides an additional DNA-binding interface. A C2H2-type zinc finger (amino acids 1632-1657) is found towards the C-terminal region, likely contributing to protein-protein or protein-nucleic acid interactions. Much of the protein consists of disordered regions, which are flexible segments that may enable the protein to adopt different conformations when interacting with various partners within the chromatin-remodelling complex. These disordered stretches are scattered throughout the sequence, including amino acids 819-844, 962-1057, 1266-1287, 1295-1314, 1321-1341, 1488-1522, and 1572-1629, as well as 1703-1728 near the C-terminus.
Key variants
Pathogenic variants in ARID2 typically result in loss of protein function, either through premature termination signals (nonsense or frameshift variants) or missense changes that disrupt critical functional domains. Because the gene follows autosomal dominant inheritance, a variant in one copy is typically sufficient to produce clinical features, though severity varies-from mild learning difficulties to more significant intellectual disability with structural anomalies. The spectrum of reported variants includes those affecting the DNA-binding domains, which may impair the protein's ability to target chromatin appropriately, as well as truncating variants that eliminate substantial portions of the protein.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.2758C>T | p.Gln920Ter | Pathogenic | ★★☆☆ | Coffin-Siris syndrome 6 |
c.3814C>T | p.Arg1272Ter | Pathogenic | ★★☆☆ | Coffin-Siris syndrome 6 |
c.400dup | p.Gln134fs | Pathogenic/Likely pathogenic | ★★☆☆ | Coffin-Siris syndrome 6 |
c.5029C>T | p.Arg1677Ter | Pathogenic/Likely pathogenic | ★★☆☆ | ARID2-related disorder |
c.5260C>T | p.Arg1754Ter | Pathogenic | ★★☆☆ | Coffin-Siris syndrome 6 |
c.5305C>T | p.Arg1769Ter | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.820C>T | p.Arg274Ter | Pathogenic/Likely pathogenic | ★★☆☆ | ARID2-related BAFopathy |
c.1121-1G>A | - | Pathogenic | ★☆☆☆ | Coffin-Siris syndrome 6 |
c.118dup | p.Val40fs | Pathogenic | ★☆☆☆ | Coffin-Siris syndrome 6 |
c.1261dup | p.Val421fs | Pathogenic | ★☆☆☆ | Coffin-Siris syndrome 6 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in ARID2 are associated with a spectrum of neurodevelopmental conditions characterised by intellectual disability, developmental delay, and structural brain anomalies. Clinical presentations can include features such as delayed speech and motor milestones, learning difficulties, and behavioural challenges. Some individuals with pathogenic ARID2 variants also exhibit congenital anomalies detectable prenatally or at birth, such as structural brain or cardiac anomalies, which has led to the gene's inclusion on foetal anomaly screening panels. The severity and specific features can vary among affected individuals, even within the same family, reflecting the complex interplay between ARID2 function and other genetic and environmental factors during development.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic ARID2 variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
Within the UK NHS Genomic Medicine Service, ARID2 appears on multiple gene panels with green classification, indicating strong evidence for clinical validity. It is included in the DDG2P panel, which catalogues genes with strong evidence for developmental disorders. The gene is also listed on the Fetal Anomalies panel for prenatal genomic investigations and the Intellectual Disability panel for postnatal diagnostic testing in individuals with cognitive impairment. These designations indicate that testing for ARID2 variants may be appropriate in clinical scenarios involving neurodevelopmental concerns or structural anomalies identified during pregnancy.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
No specific lifestyle modifications are indicated for ARID2 variants; management focuses on developmental support and symptom-specific interventions.
Supplement considerations
No supplements have been shown to modify outcomes in ARID2-related conditions. Standard nutritional guidance applies.
Frequently asked questions
What does the ARID2 gene do?
ARID2 encodes a protein that forms part of a chromatin-remodelling complex, helping to control which genes are active in cells. This regulation is especially important during brain development, where precise gene expression patterns guide the formation of neural structures.
How are ARID2 variants inherited?
ARID2 variants follow an autosomal dominant pattern, meaning an alteration in one of the two gene copies is sufficient to cause features. Each child of an affected parent has a 50% chance of inheriting the variant, though many cases arise from new (de novo) variants not present in either parent.
Are there treatments for conditions caused by ARID2 variants?
Management focuses on addressing individual symptoms and developmental needs, such as speech therapy, educational support, and behavioural interventions. There is no specific cure for ARID2-related neurodevelopmental conditions, but multidisciplinary care can help optimise outcomes and quality of life.