ARID5B
protein-codingAT-rich interaction domain 5B, the group of AT-rich interaction domain containing
Gene summary
This gene encodes a member of the AT-rich interaction domain (ARID) family of DNA binding proteins. The encoded protein forms a histone H3K9Me2 demethylase complex with PHD finger protein 2 and regulates the transcription of target genes involved in adipogenesis and liver development. This gene also plays a role in cell growth and differentiation of B-lymphocyte progenitors, and single nucleotide polymorphisms in this gene are associated with acute lymphoblastic leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~195.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007336
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ARID5B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032199.3. 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 | 15 | 3 | 19 | ||
| missense | 117 | 3 | 2 | 122 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 5 | 5 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 126 | 18 | 5 | 149 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115575.1 | 10 | MANE Select | |
| Ensembl | ENSP00000279873.7 | 10 | MANE Select | |
| RefSeq | NP_001231567.1 | 7 | Standard | |
| Ensembl | ENSP00000308862.5 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Mesodermal Commitment Pathway
- FTO Obesity Variant Mechanism
- Pathways Affected in Adenoid Cystic Carcinoma
- HDMs demethylate histones
- Chromatin modifying enzymes
Biological Process
- negative regulation of transcription by RNA polymerase II
- kidney development
- liver development
- regulation of transcription by RNA polymerase II
- male gonad development
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- DNA binding
- transcription coactivator activity
Cellular Component
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000279873
- Coding exons
- 10
- Length
- 195645
- Individuals with no LoFs
- 125667
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125670
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.60 | 478 | 667 | 0.717 | 0.0000365 | 7817 |
| Missense (PolyPhen) | 216 | 334.27 | 0.64618 | 3970 | ||
| Synonymous | 0.212 | 274 | 278 | 0.984 | 0.0000171 | 2311 |
| Loss of Function | 5.94 | 1 | 43.0 | 0.0233 | 0.00000206 | 579 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription coactivator that binds to the 5'-AATA[CT]- 3' core sequence and plays a key role in adipogenesis and liver development. Acts by forming a complex with phosphorylated PHF2, which mediates demethylation at Lys-336, leading to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2- ARID5B complex acts as a coactivator of HNF4A in liver. Required for adipogenesis: regulates triglyceride metabolism in adipocytes by regulating expression of adipogenic genes. Overexpression leads to induction of smooth muscle marker genes, suggesting that it may also act as a regulator of smooth muscle cell differentiation and proliferation. Represses the cytomegalovirus enhancer. {ECO:0000269|PubMed:21532585}.;
- Disease
- DISEASE: Note=Defects in ARID5B may be a cause of susceptibility to coronary atherosclerosis in the Japanese population.; DISEASE: Leukemia, acute lymphoblastic (ALL) [MIM:613065]: A subtype of acute leukemia, a cancer of the white blood cells. ALL is a malignant disease of bone marrow and the most common malignancy diagnosed in children. The malignant cells are lymphoid precursor cells (lymphoblasts) that are arrested in an early stage of development. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymphnodes. {ECO:0000269|PubMed:19684603, ECO:0000269|PubMed:19684604, ECO:0000269|PubMed:20042726, ECO:0000269|PubMed:20054350, ECO:0000269|PubMed:20189245, ECO:0000269|PubMed:20460642, ECO:0000269|PubMed:21098271}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- LoFtool
- 0.0665
- RVIS EVS
- -1.04
- RVIS percentile EVS
- 7.83
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.545
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |