ARID1B
protein-codingAT-rich interaction domain 1B, the group of Armadillo like helical domain containing|AT-rich interaction domain containing|BAF complex
Gene summary
This locus encodes an AT-rich DNA interacting domain-containing protein. The encoded protein is a component of the SWI/SNF chromatin remodeling complex and may play a role in cell-cycle activation. The protein encoded by this locus is similar to AT-rich interactive domain-containing protein 1A. These two proteins function as alternative, mutually exclusive ARID-subunits of the SWI/SNF complex. The associated complexes play opposing roles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~434.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007617
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007617
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0007617
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0015452
Submitter: ClinGen
ARID1B was reported in relation to autosomal dominant Coffin-Siris syndrome by three different groups around the same time in 2012 (Tsurusaki, et al., PMID: 22426308; Santen, et al., PMID: 22426309; Hoyer, et al., PMID: 22405089). Coffin-Siris syndrome is characterized by intellectual disability associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. More than 170 unique pathogenic or likely pathogenic variants in ARID1B have been reported in ClinVar, with the majority of them de novo truncating variants (van der Sluijs, et al., PMID: 30349098). Evidence supporting this gene-disease relationship includes case-level data and experimental data. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism for disease is haploinsufficiency (Hoyer, et al., PMID: 22405089). The gene-disease association is also supported by animal and cell culture models. Noteworthy, Coffin-Siris syndrome can be caused by variants in additional genes, including ARID1A, SMARCB1, SMARCA4, SMARCE1, ARID2, DPF2, SMARCC2, SOX11, and SOX4 (see OMIM). In summary, ARID1B is definitively associated with autosomal dominant Coffin-Siris syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 12/02/19 (SOP Version 7).
Inheritance Pattern: AD
Disease ID:MONDO:0015452
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0015452
Submitter: Illumina
Inheritance Pattern: AD
Disease ID:MONDO:0007617
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Dermatologic; Musculoskeletal; Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ARID1B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001374828.1. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 3 | 18 | 491 | 38 | 551 |
| missense | 4 | 24 | 807 | 387 | 43 | 1265 |
| nonsense | 141 | 44 | 7 | 192 | ||
| start loss | 0 | |||||
| frameshift | 260 | 112 | 9 | 381 | ||
| splice donor/acceptor (+/-2bp) | 22 | 19 | 14 | 1 | 56 | |
| Total | 428 | 202 | 855 | 879 | 81 | 2445 |
Highest pathogenic variant AF is 0.000030956573
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001361757.1 | 20 | MANE Select | |
| Ensembl | ENSP00000490491.2 | 20 | MANE Select | |
| RefSeq | NP_001350654.1 | 15 | Standard | |
| RefSeq | NP_001358585.1 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Thermogenesis - Homo sapiens (human)
- Hepatocellular carcinoma - Homo sapiens (human)
- Androgen Receptor Network in Prostate Cancer
- Tumor suppressor activity of SMARCB1
- Gene expression (Transcription)
Biological Process
- chromatin remodeling
- regulation of transcription by RNA polymerase II
- nervous system development
- chromatin-mediated maintenance of transcription
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- transcription coactivator activity
- protein binding
Cellular Component
- nucleoplasm
- cytosol
- plasma membrane
- SWI/SNF complex
- nBAF complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000346085
- Coding exons
- 20
- Length
- 432851
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125748
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.59 | 961 | 1.21e+3 | 0.791 | 0.0000708 | 14685 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000063 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- LoFtool
- 0.343
- RVIS EVS
- -2.62
- RVIS percentile EVS
- 0.8
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.736
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |