AT-rich interactive domain-containing protein 1A (ARID1A) (ARID1A)

AT-rich interactive domain-containing protein 1A (ARID1A) is a critical component of the SWI/SNF (BAF) chromatin-remodeling complex, which utilizes ATP-derived energy to reposition nucleosomes and regulate gene accessibility [UniProt: O14497]. It acts as a major tumor suppressor by maintaining genomic stability and controlling the expression of genes involved in cell proliferation, differentiation, and DNA repair [PMID: 20826764]. ARID1A is among the most frequently mutated genes in human cancers, with particularly high prevalence in gynecologic malignancies such as ovarian clear cell and endometrioid carcinomas [PMID: 30655315]. While ARID1A itself is typically lost through inactivating mutations, it serves as a primary therapeutic target through the principle of synthetic lethality [PMID: 31534217]. For instance, ARID1A-deficient cells exhibit a heightened dependency on the methyltransferase EZH2 and the DNA damage sensor ATR, making these proteins attractive targets for pharmacological intervention in patients harboring ARID1A mutations [PMID: 26258301, PMID: 31534217]. Consequently, ARID1A status is increasingly used as a predictive biomarker in clinical trials evaluating EZH2, PARP, and PI3K/AKT/mTOR pathway inhibitors [PMID: 28232481].

Other names

BAF250ASMARCF1OSA1P270ELDB120

Synthetic lethality targeting dependencies in ARID1A-deficient cells, such as EZH2 inhibition, ATR inhibition, or PARP inhibition.