The STAG2 gene consists of 35 exons spanning 142 Kbp, located at chromosome Xq25.

Transcription takes place in a centromere --> telomere orientation (plus strand). Transcription of STAG2 gene generates 19 different mRNA transcripts, the longest is 6045 bp containing 34 exons (ENST00000371160).
There are multiple transcription factor binding sites (TFBS) for GATA3 present in the regulatory first intron of STAG2 summarized above (Fig. 1).

There are no known pseudogenes.

The STAG2 gene encodes two alternative isoforms:
- A: Q8N3U4-1, 1231 aa, 141.3 KDa
- B: Q8N3U4-2, 1268 aa, 145.7 KDa

STAG2 mRNA is expressed in cells from most tissues. Peak expression occurs in T-cell and early erythroid compartments, and in the uterus. Lowest expression is found in brain, heart, liver, lung and testis. STAG2 is also overexpressed in T-/B-cell acute lymphoblastic leukemia (ALL) and in other hematopoietic neoplasias, followed by small cell lung cancer, neuroblastoma and medulloblastoma.
It has been reported that the expression of STAG2 protein is lost in some cancer types such as glioblastoma, Ewings sarcoma, and melanoma (Solomon et al., 2011), colorectal carcinomas, gastric carcinomas and prostate carcinomas (Kim et al., 2012).

Nucleus albeit reportedly with transmembrane potential.

STAG2 forms the cohesin complex together with SMC1, SMC3, and SCC1. The cohesin complex is a ring-like structure and is required for cohesion of sister chromatids after DNA replication. The complex is cleaved at the metaphase-anaphase transition and dissociates from chromatin for separation of sister chromatids (Xiao et al., 2011). While STAG2 mediates centromere cohesion, that of telomeres is mediated by the homologous STAG1 (Canudas et al., 2009; Remeseiro et al., 2012).
Cohesin also plays a major part in the organization of interphase chromatin, including the orchestration of gene expression in relation to cell cycle where STAG2 also plays a key role along with the universal transcriptional repressor CCCTC-binding factor (CTCF). CTCF-cohesin interactions require contact between STAG2 and C-terminal CTCF which facilitate recruitment of other cohesion complex proteins and formation of the cohesion ring. This interaction is also needed for CTCF to function as a transcriptional insulator.

Two paralogs are known: STAG1 and STAG3 which can replace STAG2 in the cohesion complex.

Recurrent STAG2 gene mutations were reported in glioblastoma, melanoma and Ewings sarcoma (Solomon et al., 2011). Recently, STAG2 gene was found frequently mutated in myeloid neoplasms, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), chronic myelogenous leukemia (CML) and classical myeloproliferative neoplasms (MPN) (Kon et al., 2013). Other studies observed lower frequencies of STAG2 mutation (Chung et al., 2012; Kim et al., 2012).
It remains unclear whether mutations affecting STAG2 operate to induce aneuploidy (Solomon et al., 2011; Kolodner et al., 2011), or simply to abrogate expression (Rocquain et al., 2010; Kon et al., 2013).