ARID1A Gene

ARID1A (AT-Rich Interaction Domain 1A) is a protein coding gene located on chromosome 1p36.11.

Diseases associated with ARID1A include Coffin-Siris syndrome 2 and Coffin-Siris syndrome 1 (Kosho Tet al. 2014). Mutations in the ARID1A gene are associated with endometriosis associated ovarian cancer (Wiegand KCet al. 2010). Furthermore, epigenetic driver mutations in the ARID1A gene in malignancies affect the immune system response to the tumor (Li J et al. 2020).

ARID1A (AT-Rich Interaction Domain 1A) encodes a member of the SWI/SNF family whose members have helicase and ATPase activities and are thought to regulate transcription of specific genes by altering chromatin structure. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. It has at least two conserved domains that may be important for its function.

Genes encoding subunits of SWI/SNF chromatin remodeling complexes are mutated in 20% of all human cancers. ARID1A is the SWI/SNF subunit gene that is most frequently mutated, with varying frequencies in all molecular and histological subtypes of cancer. When ARID1A is absent, defects in the control of enhancer activity impair developmental programs and lead to widespread dysregulation of gene expression, which in turn promotes tumor formation. The role of ARID1A has also been described in other processes associated with tumor suppression, including cell cycle/DNA damage checkpoint control, regulation of P53 targets, and telomerase activation (Mathur R 2018).

1. Kosho Tet al. (2014) Coffin-Siris Syndrome International Collaborators. Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A. Am J Med Genet C Semin Med Genet 166C:262-275.
2. Ji MM et al (2018) Histone modifier gene mutations in peripheral T-cell lymphoma not otherwise specified. Haematologica 103: 679-687.
3. Li J et al (2020) Epigenetic driver mutations in ARID1A shape cancer immune phenotype and immunotherapy. J Clin Invest 130: 2712-2726.
4. Mathur R (2018) ARID1A loss in cancer: Towards a mechanistic understanding. Pharmacol Ther 190:15-23.
5. Wiegand KCet al (2010) ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med 363:1532-1543.
6. Yabe M et al (2018) Hepatosplenic T-cell lymphoma: a review of clinicopathologic features, pathogenesis, and prognostic factors. Hum Pathol. 74:5-16.