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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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ARID4A
AT-rich interaction domain 4A
Chromosome 14 Β· 14q23.1
NCBI Gene: 5926Ensembl: ENSG00000032219.20HGNC: HGNC:9885UniProt: P29374
65PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nucleoplasmnegative regulation of DNA-templated transcriptionDNA bindingnucleussubstance-related disordermultiple myelomamigraine disordertype 2 diabetes mellitus
✦AI Summary

ARID4A is a DNA-binding protein that functions as a transcriptional co-regulator with dual roles in both repression and activation depending on cellular context 1. It operates within SIN3-histone deacetylase chr14 remodeling complexes and interacts with retinoblastoma protein (RB1) and other regulatory proteins 1. ARID4A regulates epigenetic modifications at the PWS/AS imprinting center through histone methylation and DNA methylation changes 2. Functionally, ARID4A acts as a tumor suppressor across multiple cancer types. In breast cancer, it suppresses metastasis by stabilizing mRNA transcripts of metastasis-suppressing genes including MTSS1, TIMP2, RB1, and PTEN through binding conserved 3'UTR elements 3. In prostate cancer, downregulation of ARID4A correlates with poor prognosis, high Gleason scores, and enhanced cell proliferation and invasion 4. ARID4A was also identified as a candidate neurodegeneration suppressor in ALS-FTD models, with downregulation associated with improved behavioral outcomes 5. Recently, ARID4A was identified as a novel nucleosome-binding protein 6. A schizophrenia-associated missense variant (p.His411Asp) impairs DNA-binding capacity and cell cycle regulation 7. These findings establish ARID4A as a multifunctional epigenetic regulator with therapeutic potential in cancer and psychiatric disorders.

Sources cited
1
ARID4A suppresses breast tumor metastasis by stabilizing mRNA of metastasis-suppressing genes (MTSS1, TIMP2, RB1, PTEN) through 3'UTR binding
PMID: 40066676
2
ARID4A downregulation in prostate cancer correlates with poor prognosis, high Gleason scores, and promotes cell proliferation and invasion
PMID: 29797600
3
ARID4A interacts with BRMS1 in SIN3-histone deacetylase chromatin remodeling complexes to regulate transcription and suppress metastasis
PMID: 18211900
4
ARID4A regulates epigenetic modifications at the PWS/AS imprinting center through altered histone and DNA methylation
PMID: 17043311
5
ARID4A downregulation identified as candidate suppressor of neurodegeneration in ALS-FTD model with improved behavioral outcomes
PMID: 29556029
6
Schizophrenia-associated ARID4A variant (p.His411Asp) impairs DNA-binding ability and promotes aberrant cell cycle progression
PMID: 35365808
7
ARID4A identified as a novel nucleosome-binding protein through AlphaFold-guided structural analysis
PMID: 40794873
Disease Associationsβ“˜20
substance-related disorderOpen Targets
0.30Weak
multiple myelomaOpen Targets
0.26Weak
migraine disorderOpen Targets
0.24Weak
type 2 diabetes mellitusOpen Targets
0.21Weak
mathematical abilityOpen Targets
0.17Weak
coronary artery diseaseOpen Targets
0.17Weak
attention deficit hyperactivity disorderOpen Targets
0.17Weak
substance abuseOpen Targets
0.17Weak
alcohol-related disordersOpen Targets
0.15Weak
diabetes mellitusOpen Targets
0.13Weak
venous thromboembolismOpen Targets
0.10Suggestive
coxopodopatellar syndromeOpen Targets
0.08Suggestive
Blount diseaseOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
Coxa VaraOpen Targets
0.08Suggestive
Absent tibia - polydactylyOpen Targets
0.08Suggestive
tibia, hypoplasia or aplasia of, with polydactylyOpen Targets
0.08Suggestive
breast neoplasmOpen Targets
0.07Suggestive
hip dysplasia, Beukes typeOpen Targets
0.07Suggestive
metaphyseal anadysplasiaOpen Targets
0.07Suggestive
Pathogenic Variants1
NM_002892.4(ARID4A):c.2614G>T (p.Glu872Ter)Likely pathogenic
Multiple myeloma
β˜†β˜†β˜†β˜†2019β†’ Residue 872
View on ClinVar β†—
Related Genes
H3C13Protein interaction100%H3C12Protein interaction100%SAP30Protein interaction100%HDAC1Protein interaction99%RBL1Protein interaction97%ACTL6AProtein interaction96%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
27%
Heart
26%
Liver
24%
Ovary
21%
Lung
21%
Gene Interaction Network
Click a node to explore
ARID4AH3C13H3C12SAP30HDAC1RBL1ACTL6A
PROTEIN STRUCTURE
Preparing viewer…
PDB6BPH Β· 1.85 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.34Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.24 [0.18–0.34]
RankingsWhere ARID4A stands among ~20K protein-coding genes
  • #7,145of 20,598
    Most Researched65
  • #5,019of 5,498
    Most Pathogenic Variants1
  • #1,457of 17,882
    Most Constrained (LOEUF)0.34 Β· top 10%
Genes detectedARID4A
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD.
PMID: 29556029
Nat Neurosci Β· 2018
1.00
2
Arid4a Suppresses Breast Tumor Metastasis by Enhancing MTSS1 Expression via mRNA Stability.
PMID: 40066676
Cancer Med Β· 2025
0.90
3
Downregulation of ARID4A and ARID4B promote tumor progression and directly regulated by microRNA-30d in patient with prostate cancer.
PMID: 29797600
J Cell Biochem Β· 2018
0.80
4
Alterations of BRMS1-ARID4A interaction modify gene expression but still suppress metastasis in human breast cancer cells.
PMID: 18211900
J Biol Chem Β· 2008
0.70
5
Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and suppresses an imprinting defect in the PWS/AS domain.
PMID: 17043311
Genes Dev Β· 2006
0.60