STAG2: Cohesin Complex Subunit SA-2
A key regulator of sister chromatid cohesion, gene expression, and DNA repair; frequently mutated in cancer and associated with neurodevelopmental disorders.
Gene Information Card
| Symbol | STAG2 |
|---|---|
| Full Name | Stromal Antigen 2 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq25 |
| NCBI Gene ID | 10735 ncbi.nlm.nih.gov/gene/10735 |
| Ensembl ID | ENSG00000101972 |
| UniProt ID | Q8N3U4 |
| OMIM ID | 300826 |
| HGNC ID | 11355 |
| Aliases | SA-2, SA2, SCC3B, bA517O1.1 |
Description
STAG2 encodes the stromal antigen 2 protein, a subunit of the cohesin complex. The cohesin complex forms a ring-like structure that holds sister chromatids together after DNA replication, ensuring proper chromosome segregation during mitosis and meiosis. Beyond cohesion, STAG2 is involved in DNA double-strand break repair, transcriptional regulation, and chromatin looping. Loss-of-function mutations in STAG2 are recurrent in multiple cancer types, including bladder cancer, Ewing sarcoma, and myeloid neoplasms, and germline variants are associated with neurodevelopmental disorders such as Cornelia de Lange syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bladder cancer | Inactivating mutations (nonsense, frameshift, splice site) lead to loss of STAG2 protein, causing chromosomal instability and aneuploidy. | Recurrent somatic mutations in ~6-10% of bladder cancers (COSMIC, ClinVar). |
| Ewing sarcoma | STAG2 mutations co-occur with EWSR1-FLI1 fusion; loss of STAG2 promotes metastasis and alters gene expression. | Found in ~15-20% of Ewing sarcoma cases (COSMIC, NCBI). |
| Cornelia de Lange syndrome (CdLS) | Germline missense or loss-of-function variants in STAG2 disrupt cohesin function, leading to developmental defects. | Rare; reported in multiple families (OMIM #300826, ClinVar). |
| Myelodysplastic syndromes (MDS) | Somatic STAG2 mutations contribute to dysplastic hematopoiesis and increased risk of leukemic transformation. | Detected in ~5-10% of MDS cases (COSMIC, NCBI). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.2 | High |
| Bone marrow | 25.1 | Medium |
| Lymph node | 22.8 | Medium |
| Brain (cortex) | 18.5 | Medium |
| Liver | 12.3 | Medium |
| Heart | 10.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 32.5 | High expression; used in functional studies |
| K562 (leukemia) | 28.7 | Medium expression |
| A549 (lung carcinoma) | 22.1 | Medium expression |
| MCF7 (breast carcinoma) | 19.4 | Medium expression |
| HCT116 (colorectal carcinoma) | 15.6 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2065C>T (p.Gln689*) | Nonsense | Recurrent in bladder cancer | Loss of function; truncated protein |
| c.1111_1112del (p.Glu371fs) | Frameshift | Recurrent in Ewing sarcoma | Loss of function; premature stop |
| c.2041+1G>A | Splice site | Reported in MDS | Loss of function; aberrant splicing |
| c.1873G>A (p.Gly625Arg) | Missense | Rare germline in CdLS | Dominant-negative effect on cohesin loading |
Mutation functional classification
Loss of Function (LOF)
Most common mechanism; nonsense, frameshift, and splice-site mutations lead to truncated or absent STAG2 protein, impairing cohesin complex stability and function.
Gain of Function (GOF)
Not described for STAG2; no activating mutations have been reported.
Dominant Negative (DN)
Rare missense variants (e.g., p.Gly625Arg) in the stromalin domain can interfere with wild-type STAG2 incorporation into the cohesin complex, causing dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cell Cycle – Sister Chromatid Cohesion (Reactome: R-HSA-1500620)
• DNA Double-Strand Break Repair (Reactome: R-HSA-5693606)
• Chromatin Organization (Reactome: R-HSA-2299718)
Protein Summary
STAG2 (stromal antigen 2) is a 1231-amino-acid protein that serves as a structural component of the cohesin complex. It contains a conserved stromalin domain and interacts with SMC1, SMC3, and RAD21 to form the cohesin ring. STAG2 is ubiquitously expressed but shows highest levels in testis and bone marrow. The protein is essential for proper chromosome segregation, DNA repair, and transcriptional regulation. Loss of STAG2 leads to cohesion defects, aneuploidy, and altered gene expression profiles, contributing to tumorigenesis and developmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STAG2 Knockout HEK293 Cell Line | EDJ-KQ3281 | Human | 10735 | Details Get a Quote |
| STAG2 Knockout A-549 Cell Line | EDJ-KQ17934 | Human | 10735 | Details Get a Quote |
| STAG2 Knockout HCT 116 Cell Line | EDJ-KQ24836 | Human | 10735 | Details Get a Quote |
| STAG2 Knockout HeLa Cell Line | EDJ-KQ24837 | Human | 10735 | Details Get a Quote |
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