ARID1B

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

Basic information

Region (hg38): 6:156776019-157210779

Links

ENSG00000049618 ∙ NCBI:57492 ∙ OMIM:614556 ∙ HGNC:18040 ∙ Uniprot:Q8NFD5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Coffin-Siris syndrome (Definitive), mode of inheritance: AD
• Coffin-Siris syndrome 1 (Definitive), mode of inheritance: AD
• Coffin-Siris syndrome 1 (Strong), mode of inheritance: AD
• Coffin-Siris syndrome 1 (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 1	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	22405089; 22426308; 22426309

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARID1B gene.

• not provided (1246 variants)
• Inborn genetic diseases (450 variants)
• Coffin-Siris syndrome 1 (360 variants)
• not specified (143 variants)
• ARID1B-related BAFopathy (47 variants)
• ARID1B-related condition (33 variants)
• Intellectual disability (15 variants)
• See cases (10 variants)
• Coffin-Siris syndrome (5 variants)
• 6 conditions (5 variants)
• Coffin Siris/Intellectual Disability (4 variants)
• ARID1B-related disorder (3 variants)
• Global developmental delay (2 variants)
• Neurodevelopmental disorder (2 variants)
• Neurodevelopmental delay (2 variants)
• Marfanoid habitus and intellectual disability (2 variants)
• Seizure (2 variants)
• Adrenal cortex carcinoma (1 variants)
• 7 conditions (1 variants)
• Developmental disorder (1 variants)
• Microcephaly (1 variants)
• Corpus callosum, agenesis of;Neonatal hypotonia;Hypertrichosis;Nail dysplasia;Global developmental delay (1 variants)
• Congenital cerebellar hypoplasia;Corpus callosum, agenesis of (1 variants)
• Rare genetic intellectual disability (1 variants)
• Pituitary stalk interruption syndrome (1 variants)
• Astrocytoma (1 variants)
• 10 conditions (1 variants)
• Seizure;Intellectual disability (1 variants)
• Autism spectrum disorder (1 variants)
• Medulloblastoma (1 variants)
• Nicolaides-Baraitser syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARID1B 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			14	250	31	295
missense	1	15	462	141	32	651
nonsense	105	21				126
start loss			1			1
frameshift	176	51	2			229
inframe indel		1	50	91	5	147
splice donor/acceptor (+/-2bp)	17	9	2	1		29
splice region		2	6	12	4	24
non coding	1		5	66	41	113
Total	300	97	536	549	109

Highest pathogenic variant AF is 0.0000551

Variants in ARID1B

This is a list of pathogenic ClinVar variants found in the ARID1B region.

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

Position	Type	Phenotype	Significance	ClinVar
6-156777692-G-GGCA			Benign (Nov 26, 2019)
6-156777698-AGCG-A		Coffin-Siris syndrome 1	Uncertain significance (-)
6-156777698-AGCGGCGGCG-A			Likely benign (Feb 01, 2024)
6-156777698-A-AGCGGCGGCG			Likely benign (Sep 24, 2019)
6-156777698-A-AGCGGCGGCGGCGGCGGCG			Uncertain significance (Aug 28, 2023)
6-156777701-G-A			Likely benign (Nov 01, 2023)
6-156777718-CGGCGCGGGCGCG-C			Likely benign (Oct 01, 2023)
6-156777818-C-CGCG			Likely benign (Mar 01, 2024)
6-156777879-G-A			Benign (Aug 31, 2018)
6-156777890-T-G			Benign/Likely benign (Feb 01, 2024)
6-156777927-A-G		not specified	Conflicting classifications of pathogenicity (Jul 01, 2022)
6-156777933-G-T		Coffin-Siris syndrome 1	Uncertain significance (Aug 12, 2019)
6-156777936-C-T			Uncertain significance (Oct 02, 2022)
6-156777938-T-A			Uncertain significance (Nov 13, 2023)
6-156777940-A-ACGCGGGCGC		not specified • Inborn genetic diseases	Likely benign (Aug 17, 2023)
6-156777946-G-A		Coffin-Siris syndrome 1 • ARID1B-related BAFopathy	Likely pathogenic (Jun 10, 2021)
6-156777949-C-G		ARID1B-related disorder	Uncertain significance (Feb 15, 2024)
6-156777949-C-T			Benign (Aug 03, 2022)
6-156777951-G-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 15, 2023)
6-156777954-G-A			Benign (Feb 16, 2023)
6-156777955-C-G		ARID1B-related disorder	Uncertain significance (Oct 10, 2023)
6-156777955-C-T			Benign (Jan 08, 2024)
6-156777963-G-A		not specified	Conflicting classifications of pathogenicity (Sep 19, 2023)
6-156777972-A-G		Inborn genetic diseases • Coffin-Siris syndrome 1	Uncertain significance (Nov 24, 2023)
6-156777975-G-A			Uncertain significance (Oct 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARID1B	protein_coding	protein_coding	ENST00000346085	20	432851

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.04e-12	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.59	961	1.21e+3	0.791	0.0000708	14685
Missense in Polyphen		429	629.59	0.6814		7099
Synonymous	-0.120	507	504	1.01	0.0000349	4450
Loss of Function	8.41	4	90.1	0.0444	0.00000481	980

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000626	0.0000626
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000529	0.0000352
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. 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). Binds DNA non-specifically (PubMed:14982958, PubMed:15170388). {ECO:0000250|UniProtKB:E9Q4N7, ECO:0000269|PubMed:14982958, ECO:0000269|PubMed:15170388, ECO:0000303|PubMed:12672490, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.
• Disease: DISEASE: Coffin-Siris syndrome 1 (CSS1) [MIM:135900]: 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. {ECO:0000269|PubMed:22405089, ECO:0000269|PubMed:22426308, ECO:0000269|PubMed:22426309}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thermogenesis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Androgen Receptor Network in Prostate Cancer;Tumor suppressor activity of SMARCB1;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Generic Transcription Pathway;RNA Polymerase II Transcription;RMTs methylate histone arginines;Chromatin modifying enzymes;Chromatin organization;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.343
• rvis_EVS: -2.62
• rvis_percentile_EVS: 0.8

Haploinsufficiency Scores

• pHI: 0.152
• hipred: Y
• hipred_score: 0.646
• ghis: 0.651

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.736

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arid1b
• Phenotype: renal/urinary system phenotype; immune system 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); 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: chromatin remodeling;regulation of transcription by RNA polymerase II;nervous system development;chromatin-mediated maintenance of transcription
• Cellular component: nucleoplasm;cytosol;plasma membrane;SWI/SNF complex;nBAF complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;transcription coactivator activity;protein binding