Cohesin subunit SA-2 (STAG2)

Cohesin subunit SA-2 (STAG2) is a protein encoded by the STAG2 gene on the X chromosome and serves as a critical component of the cohesin complex. This complex regulates sister chromatid cohesion, homologous recombination, DNA looping, chromatin organization, transcription, DNA repair, and gene expression. In somatic cells, cohesin includes SMC3, SMC1, RAD21, and either SA1 or SA2 (STAG2)[1][5]. STAG2 mutations are common in multiple human cancers, notably bladder cancer, glioblastoma, Ewing sarcoma, and some leukemias, where they can serve as biomarkers or affect prognosis[1][2]. STAG2 also plays a non-redundant role in regulating hematopoietic differentiation and suppression of transformation, and its loss disrupts lineage specification and can result in neurodevelopmental disorders when mutated in the germline[2][1][4]. Currently, therapeutic efforts focus on exploiting vulnerabilities in STAG2-deficient cancers, especially through synthetic lethality with STAG1 inhibition[2]. Therapeutic targeting faces safety challenges due to fundamental roles in chromosome segregation and cell viability[2].

Other names

STAG2SA-2SA2SCC3BStromal antigen 2SCC3 homolog 2sister chromatid cohesion 3 homolog BSA2 stromalinbA517O1.1NEDXCFMKMSHPE13

Synthetic lethality: Targeting STAG1 or core cohesin components in cells lacking STAG2 induces cell death. Disruption of cohesin-mediated chromatin architecture impairs cell division and transcription leading to cell death, especially in cancer cells harboring STAG2 mutations.