ARID4A
protein-codingAT-rich interaction domain 4A, the group of AT-rich interaction domain containing
Gene summary
The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein (pRB) which regulates cell proliferation. pRB represses transcription by recruiting the encoded protein. This protein, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function. The encoded protein possesses transcriptional repression activity. Multiple alternatively spliced transcripts have been observed for this gene, although not all transcript variants have been fully described. [provided by RefSeq, Jul 2008]
- RBBP1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~75.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ARID4A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002892.4. 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 | 1 | ||||
| missense | 135 | 4 | 139 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 3 | |||
| Total | 0 | 1 | 139 | 5 | 0 | 145 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002883.3 | 23 | MANE Select | |
| Ensembl | ENSP00000347602.3 | 23 | MANE Select | |
| RefSeq | NP_075376.2 | 23 | Standard | |
| RefSeq | NP_075377.2 | 22 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- HDACs deacetylate histones
- Chromatin modifying enzymes
- Chromatin organization
Biological Process
- regulation of gene expression by genetic imprinting
- regulation of transcription by RNA polymerase II
- spermatogenesis
- histone deacetylation
- histone H4-K20 trimethylation
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- histone deacetylase activity
- transcription regulatory region DNA binding
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- plasma membrane
- transcriptional repressor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000355431
- Coding exons
- 23
- Length
- 75503
- Individuals with no LoFs
- 124754
- Homozygous LoFs
- 5
- Heterozygous LoFs
- 985
- Defined
- 125744
- p
- 0.00394
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.45 | 524 | 626 | 0.837 | 0.0000306 | 8339 |
| Missense (PolyPhen) | 181 | 279.54 | 0.64749 | 3624 | ||
| Synonymous | 0.295 | 211 | 217 | 0.974 | 0.0000110 | 2189 |
| Loss of Function | 7.06 | 4 | 65.9 | 0.0607 | 0.00000360 | 885 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0012 | 0.0012 | notable |
| Latino/Admixed American | 0.0019 | 0.0018 | notable |
| Ashkenazi Jewish | 0.0093 | 0.0082 | notable |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.0038 | 0.0037 | notable |
| European (Non-Finnish) | 0.0060 | 0.0056 | notable |
| South Asian | 0.0030 | 0.0027 | notable |
| Other | 0.0044 | 0.0041 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (By similarity). May function as part of an mSin3A repressor complex (PubMed:14581478). Has no intrinsic transcriptional activity (By similarity). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B (By similarity). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (By similarity). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity). {ECO:0000250|UniProtKB:F8VPQ2, ECO:0000269|PubMed:14581478}.;
Recessive Scores
- pRec
- 0.211
Intolerance Scores
- LoFtool
- 0.351
- RVIS EVS
- -1.19
- RVIS percentile EVS
- 5.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.898
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |