ARID1A

AT-rich interaction domain 1A, the group of BAF complex|AT-rich interaction domain containing|Armadillo like helical domain containing

Basic information

Region (hg38): 1:26693235-26782104

Previous symbols: [ "C1orf4", "SMARCF1" ]

Links

ENSG00000117713 ∙ NCBI:8289 ∙ OMIM:603024 ∙ HGNC:11110 ∙ Uniprot:O14497 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 14 (Strong), mode of inheritance: AD
• Coffin-Siris syndrome 1 (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 14 (Strong), mode of inheritance: AD
• Coffin-Siris syndrome (Supportive), mode of inheritance: AD
• Coffin-Siris syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Coffin-Siris syndrome 2 (Mental retardation, autosomal dominant 14)	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	22426308; 22426309

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARID1A gene.

• not provided (725 variants)
• Intellectual disability, autosomal dominant 14 (152 variants)
• not specified (96 variants)
• Inborn genetic diseases (78 variants)
• ARID1A-related condition (23 variants)
• ARID1A-related BAFopathy (10 variants)
• Intellectual disability (4 variants)
• Coffin-Siris syndrome 1 (3 variants)
• Neurodevelopmental delay (2 variants)
• Coffin-Siris syndrome (1 variants)
• Septo-optic dysplasia sequence (1 variants)
• Pulmonic stenosis;Intellectual disability (1 variants)
• Neurodevelopmental disorder (1 variants)
• Autism spectrum disorder (1 variants)
• 6 conditions (1 variants)
• Non-immune hydrops fetalis (1 variants)
• Marfanoid habitus and intellectual disability (1 variants)
• Seizure (1 variants)
• Astrocytoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARID1A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			19	154	38	211
missense	2	18	325	81	44	470
nonsense	21	5				26
start loss			2			2
frameshift	14	9				23
inframe indel		2	25	15	1	43
splice donor/acceptor (+/-2bp)	2	1	1			4
splice region		2	7	8	2	19
non coding			4	42	26	72
Total	39	35	376	292	109

Variants in ARID1A

This is a list of pathogenic ClinVar variants found in the ARID1A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-26695829-G-A			Likely benign (Apr 04, 2019)
1-26695894-T-C			Likely benign (Nov 10, 2018)
1-26696377-C-T			Benign (Mar 26, 2020)
1-26696397-G-T		not specified	Uncertain significance (Jun 21, 2016)
1-26696405-T-C			Uncertain significance (Aug 07, 2020)
1-26696405-T-G			Uncertain significance (Sep 16, 2022)
1-26696407-G-A			Uncertain significance (Jun 15, 2023)
1-26696416-G-A			Uncertain significance (Aug 05, 2023)
1-26696421-CCCCGCCGCCGCCAGCAGCCTGGGCAA-C		Intellectual disability, autosomal dominant 14 • Coffin-Siris syndrome 1	Pathogenic (May 15, 2023)
1-26696425-G-A			Uncertain significance (Jul 06, 2020)
1-26696427-C-G			Likely benign (Jan 16, 2024)
1-26696439-C-T		ARID1A-related disorder	Benign/Likely benign (Jan 12, 2024)
1-26696448-CCCG-C		ARID1A-related disorder	Benign/Likely benign (Sep 12, 2023)
1-26696448-CCCGCCG-C			Likely benign (Jul 11, 2022)
1-26696448-C-CCCG		not specified • Astrocytoma • Inborn genetic diseases • ARID1A-related disorder	Conflicting classifications of pathogenicity (Feb 01, 2024)
1-26696448-C-CCCGCCG		Inborn genetic diseases • ARID1A-related disorder	Benign/Likely benign (Jan 11, 2024)
1-26696458-C-G			Uncertain significance (Sep 01, 2019)
1-26696463-G-A			Likely benign (Jan 01, 2023)
1-26696469-G-C			Likely benign (May 04, 2021)
1-26696470-G-T			Uncertain significance (Sep 16, 2018)
1-26696475-G-C			Likely benign (Aug 10, 2021)
1-26696478-G-A			Benign (Jun 29, 2023)
1-26696484-C-T		ARID1A-related disorder	Likely benign (Dec 14, 2020)
1-26696494-C-G		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)
1-26696495-AGCGGGAGGAG-A		Intellectual disability, autosomal dominant 14	Conflicting classifications of pathogenicity (Apr 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARID1A	protein_coding	protein_coding	ENST00000324856	20	86072

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.67e-13	125745	0	2	125747	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.66	823	1.18e+3	0.700	0.0000669	14782
Missense in Polyphen		44	120.16	0.36619		1335
Synonymous	-1.27	494	459	1.08	0.0000269	4683
Loss of Function	8.55	2	89.0	0.0225	0.00000473	980

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. Binds DNA non-specifically. 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 (By similarity). {ECO:0000250|UniProtKB:A2BH40, ECO:0000303|PubMed:12672490, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.
• Pathway: Thermogenesis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Androgen Receptor Network in Prostate Cancer;Pathways Affected in Adenoid Cystic Carcinoma;Tumor suppressor activity of SMARCB1;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;the information processing pathway at the ifn beta enhancer;Generic Transcription Pathway;RNA Polymerase II Transcription;RMTs methylate histone arginines;Chromatin modifying enzymes;Chromatin organization;chromatin remodeling by hswi/snf atp-dependent complexes;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.151

Intolerance Scores

• loftool: 0.0215
• rvis_EVS: -2.67
• rvis_percentile_EVS: 0.74

Haploinsufficiency Scores

• pHI: 0.549
• hipred: Y
• hipred_score: 0.783
• ghis: 0.683

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.942

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Arid1a
• Phenotype: immune system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; embryo phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;formation of primary germ layer;neural tube closure;cardiac chamber development;optic cup formation involved in camera-type eye development;nucleosome disassembly;chromatin remodeling;maintenance of chromatin silencing;regulation of transcription by RNA polymerase II;embryo implantation;stem cell population maintenance;intracellular estrogen receptor signaling pathway;androgen receptor signaling pathway;forebrain development;nucleosome mobilization;glucocorticoid receptor signaling pathway;ATP-dependent chromatin remodeling;positive regulation of transcription, DNA-templated;chromatin-mediated maintenance of transcription;cardiac muscle cell differentiation;placenta blood vessel development;toxin transport
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;SWI/SNF complex;npBAF complex;nBAF complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;transcription coactivator activity;protein binding;nuclear receptor binding;nucleosome binding