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STAG2 is frequently mutated in a range of cancers and several other disorders.
Function
SA2 is part of the cohesin complex, which is a structure that holds the sister chromatids together after DNA replication. STAG2 has been shown to interact with STAG1. Cohesion folds by DNA loop extrusion and this cohesion consists of SMC1, SMC3, RAD21, and either STAG1 or STAG2. SA2 interacts with a ring-like structure composed of SMC1A, SMC3, and RAD21, to form the core of the cohesin complex. The ring-like structure binds chromosomes together until degradation of the cohesin complex is finished during cell division. This allows for the replicated chromosomes to separate into two new cells. Another role of STAG2 is to encode the stromal antigen 2 protein, which is involved in chromatin organization, transcription, DNA repair and control of downstream gene expression.
Structure
Of the cohesin complex, STAG2 is the subunit where the most variants have been reported in cancer. This is thought to be because this gene is located in the X chromosome, therefore only one mutation is needed to inactivate it. Xq25 duplication syndrome, is an X-linked neurodevelopmental disorder that results in delayed development and intellectual disability associated with abnormal behavior and dysmorphic facial features, and the whole STAG2 gene can develop STAG2encephalopathy. This has all the symptoms of epilepsy with eyelid myoclonia and absences (EMA), and was formally named Jeavons syndrome (JS).
Mutations
One result of mutations in STAG2 can result in one third of non-muscle-invasive bladder cancer to have complete loss of SA2 protein. The loss of this protein has been shown to indicate the prognosis of disease and survival. it has been shown there was a delay in maturation of oligodendrocytes and transcription of myelination-related genes was reduced. Cohesion is needed in proper gene expression in specific cells and an implication the myelination is affected in a negative way. Mutations of STAG2 occur frequently in many cancers, which indicates this protein has a role in cancer. Mutations of the STAG2 gene are frequently seen in multiple adult and pediatric cancers. STAG has been found to be the only gene of 12 that is mutated significantly in at least four types of cancers.
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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Turchi G, Bernardo P, Consales A, Bilo L, Coppola A (April 2020). "Xq25 microduplication syndrome: a further contribution to its definition. A case report and review of the literature". Clinical Dysmorphology. 29 (2): 90–96. doi:10.1097/mcd.0000000000000303. PMID31609727. S2CID204703545.
Gokce-Samar Z, de Bellescize J, Arzimanoglou A, Putoux A, Chatron N, Lesca G, Portes VD (December 2022). "STAG2 microduplication in a patient with eyelid myoclonia and absences and a review of EMA-related reported genes". European Journal of Medical Genetics. 65 (12): 104636. doi:10.1016/j.ejmg.2022.104636. PMID36216271. S2CID252792610.
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