STAG2

STAG2, also known as SA2 (Stromal Antigen 2), is a gene that encodes a regulatory subunit of the cohesin complex. The cohesin complex is a multi-protein machine that mediates sister chromatid cohesion during cell division, participates in DNA repair, and contributes to the control of gene expression through chromatin organization. STAG2 is one of two STAG subunits; the complex can contain either STAG2 (SA2) or STAG1 (SA1) as the fourth subunit alongside SMC1A, SMC3, and RAD21. STAG2 is located on the X chromosome and is expressed in a wide range of tissues.

Functionally, STAG2-containing cohesin establishes and maintains sister chromatid cohesion during the cell cycle, which is essential for accurate chromosome segregation and genomic stability. The protein also influences higher-order chromatin structure and transcriptional regulation by shaping chromatin loops and topologically associating domains, thereby affecting gene expression programs.

In clinical contexts, STAG2 is frequently inactivated by somatic mutations, deletions, or loss of protein expression in various cancers. The most well-described setting is urothelial (bladder) carcinoma, with additional alterations reported in glioblastoma, Ewing sarcoma, and other tumors. As a tumor suppressor, loss of STAG2 function can contribute to chromosomal instability through defective cohesin activity; detection of STAG2 status can be performed by sequencing or immunohistochemistry for protein expression.

Germline STAG2 variants are rare. Most reported alterations in patients are somatic and studied for their diagnostic or prognostic implications. In model systems, complete loss of STAG2 disrupts cell division, and in some contexts, STAG1 can partially compensate, reflecting functional redundancy within the cohesin complex.