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): 6:156776020-157210779

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 (1895 variants)
• Inborn_genetic_diseases (569 variants)
• Coffin-Siris_syndrome_1 (490 variants)
• ARID1B-related_disorder (216 variants)
• not_specified (168 variants)
• ARID1B-related_BAFopathy (47 variants)
• Intellectual_disability (28 variants)
• Coffin-Siris_syndrome (21 variants)
• See_cases (9 variants)
• Long_eyelashes (4 variants)
• Blepharophimosis (4 variants)
• Thin_upper_lip_vermilion (4 variants)
• Moderate_intellectual_disability (4 variants)
• Coffin_Siris/Intellectual_Disability (4 variants)
• Global_developmental_delay (4 variants)
• Thick_lower_lip_vermilion (4 variants)
• Absent_speech (4 variants)
• Neurodevelopmental_disorder (3 variants)
• Severe_combined_immunodeficiency_due_to_DCLRE1C_deficiency (3 variants)
• Corpus_callosum,_agenesis_of (2 variants)
• Autism_spectrum_disorder (2 variants)
• Microcephaly (2 variants)
• Hypertrichosis (2 variants)
• Neurodevelopmental_delay (2 variants)
• Marfanoid_habitus_and_intellectual_disability (2 variants)
• Developmental_disorder (2 variants)
• dysmorphy (1 variants)
• Pituitary_stalk_interruption_syndrome (1 variants)
• Abnormal_speech_pattern (1 variants)
• Delayed_speech_and_language_development (1 variants)
• Rare_genetic_intellectual_disability (1 variants)
• Nicolaides-Baraitser_syndrome (1 variants)
• Neonatal_hypotonia (1 variants)
• Seizure (1 variants)
• Constipation (1 variants)
• Hirsutism (1 variants)
• Noonan_syndrome (1 variants)
• Short_stature (1 variants)
• Medulloblastoma (1 variants)
• Wiedemann-Steiner_syndrome (1 variants)
• intellectual_deficiency (1 variants)
• Decreased_body_weight (1 variants)
• Epilepsy (1 variants)
• Schizophrenia (1 variants)
• Bilateral_cryptorchidism (1 variants)
• Recurrent_respiratory_infections (1 variants)
• Hereditary_ataxia (1 variants)
• Metabolic_disease (1 variants)
• Neurodevelopmental_abnormality (1 variants)
• Nail_dysplasia (1 variants)
• Astrocytoma (1 variants)
• Neurofibromatosis,_type_1 (1 variants)
• Congenital_cerebellar_hypoplasia (1 variants)
• Failure_to_thrive (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. These statistics are base on transcript: NM_001374828.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	2	3	17	438	42	502
missense	14	25	699	346	42	1126
nonsense	138	35	7			180
start loss						0
frameshift	249	84	10			343
splice donor/acceptor (+/-2bp)	23	17	11	1		52
Total	426	164	744	785	84

Highest pathogenic variant AF is 0.000030956573

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
		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

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

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