Atlas of Genetics and Cytogenetics in Oncology and Haematology

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STAG2 (Stromal Antigen 2)

Written2013-09Suning Chen, Stefan Nagel, Hans G Drexler, Roderick AF MacLeod
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis, Hemostasis of Ministry of Health, the First Affiliated Hospital of Soochow University, Suzhou, P R China (SC); Department of Human, Animal Cell Lines, Leibniz-Institute DSMZ-German Collection of Microorganisms, Cell Cultures, Braunschweig, Germany (SN, HGD, RAFM)

(Note : for Links provided by Atlas : click)


Alias (NCBI)SA-2
HGNC Alias symbSA-2
LocusID (NCBI) 10735
Atlas_Id 52377
Location Xq25  [Link to chromosome band Xq25]
Location_base_pair Starts at 123961706 and ends at 124102655 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping STAG2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
LSM14A (19q13.11)::STAG2 (Xq25)NELFE (6p21.33)::STAG2 (Xq25)STAG2 (Xq25)::ATRX (Xq21.1)
STAG2 (Xq25)::C16orf45 (16p13.11)STAG2 (Xq25)::CMC4 (Xq28)STAG2 (Xq25)::EIF3A (10q26.11)
STAG2 (Xq25)::GRIA3 (Xq25)STAG2 (Xq25)::STAG2 (Xq25)STAG2 (Xq25)::XIAP (Xq25)
XIAP (Xq25)::STAG2 (Xq25)


  Figure 1. Clustering of GATA3 TFBS in STAG2 regulatory region. Schema showing multiple GATA3 TFBS present in the regulatory intron of STAG2. For additional TFBS see: SABiosciences
Description The STAG2 gene consists of 35 exons spanning 142 Kbp, located at chromosome Xq25.
Transcription 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).
Pseudogene There are no known pseudogenes.


Description The STAG2 gene encodes two alternative isoforms:
- A: Q8N3U4-1, 1231 aa, 141.3 KDa
- B: Q8N3U4-2, 1268 aa, 145.7 KDa
  Figure 2. Domain structure of STAG2 and amino acid sequence.
Expression 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, Ewing's sarcoma, and melanoma (Solomon et al., 2011), colorectal carcinomas, gastric carcinomas and prostate carcinomas (Kim et al., 2012).
Localisation Nucleus albeit reportedly with transmembrane potential.
Function 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.
Homology Two paralogs are known: STAG1 and STAG3 which can replace STAG2 in the cohesion complex.


Note Recurrent STAG2 gene mutations were reported in glioblastoma, melanoma and Ewing's 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).

Implicated in

Entity Myeloid neoplasms
Note Mutation and deletion of the STAG2 gene was identified in 5.8% (13/224) of MDS, 10.2% (9/88) of CMML, 6.4% (10/157) of AML, 3.1% (2/64) of CML, and 1.3% (1/77) of MPN: the STAG2 alterations were mostly exclusive with alterations involving other components of cohesin complex (SMC1, SMC3, and RAD21) and were significantly associated with mutations in TET2, ASXL1, and EZH2 (Kon et al., 2013).
Entity t(X;11)(q25;p13)
Disease T-ALL: only two T-ALL cell lines described so far.
Cytogenetics t(X;11)(q25;p13) in MOLT-14 cells and t(X;1;11)(q25;p13;p13) in PER-117 cells. The rearrangement is fully cryptic (see below).
Figure 4. Cytogenetic analysis of t(X;11) effecting juxtaposition of STAG2 and LMO2. Image shows FISH analysis of t(X;11)(q25;p13) in a T-ALL cell line (DSM ACC 437). Note that this translocation is cryptic in G-banding (Fig. A). FISH using BAC and fosmid clones (Fig. B, C) places breakpoints in MOLT-14 and another T-ALL cell line PER-117, both inside the first (regulatory) intron of STAG2. In both cell lines expression of STAG2 is lost, attributable to divestment of this region which includes a deeply conserved cluster of regulatory motifs, including transcription factor binding sites and DNaseI sensitive sites. Upregulation of LMO2 in both cell lines occurred, concomitant with acquisition of the upstream STAG2 region. Fig. D: Genomic map of Xq25 showing breakpoints in regulatory region in relation to clones used for FISH. Figure redrawn and updated from Chen et al. (2011).
Oncogenesis t(X;11)(q25;p13) results in simultaneous upregulation of LMO2 and silencing of STAG2 by juxtaposition of the far upstream region of LMO2 with the first regulatory intron of STAG2 (Chen et al., 2011).


Differential regulation of telomere and centromere cohesion by the Scc3 homologues SA1 and SA2, respectively, in human cells.
Canudas S, Smith S.
J Cell Biol. 2009 Oct 19;187(2):165-73. doi: 10.1083/jcb.200903096. Epub 2009 Oct 12.
PMID 19822671
Novel non-TCR chromosome translocations t(3;11)(q25;p13) and t(X;11)(q25;p13) activating LMO2 by juxtaposition with MBNL1 and STAG2.
Chen S, Nagel S, Schneider B, Kaufmann M, Meyer C, Zaborski M, Kees UR, Drexler HG, MacLeod RA.
Leukemia. 2011 Oct;25(10):1632-5. doi: 10.1038/leu.2011.119. Epub 2011 Jun 7.
PMID 21647158
Somatic mutation of STAG2, an aneuploidy-related gene, is rare in acute leukemias.
Chung NG, Kim MS, Yoo NJ, Lee SH.
Leuk Lymphoma. 2012 Jun;53(6):1234-5. doi: 10.3109/10428194.2011.645819. Epub 2012 Jan 3.
PMID 22132872
Condensin and cohesin: more than chromosome compactor and glue.
Hagstrom KA, Meyer BJ.
Nat Rev Genet. 2003 Jul;4(7):520-34. (REVIEW)
PMID 12838344
Mutational and expressional analyses of STAG2 gene in solid cancers.
Kim MS, Kim SS, Je EM, Yoo NJ, Lee SH.
Neoplasma. 2012;59(5):524-9. doi: 10.4149/neo_2012_067.
PMID 22668012
Cancer. Aneuploidy drives a mutator phenotype in cancer.
Kolodner RD, Cleveland DW, Putnam CD.
Science. 2011 Aug 19;333(6045):942-3. doi: 10.1126/science.1211154.
PMID 21852477
Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms.
Kon A, Shih LY, Minamino M, Sanada M, Shiraishi Y, Nagata Y, Yoshida K, Okuno Y, Bando M, Nakato R, Ishikawa S, Sato-Otsubo A, Nagae G, Nishimoto A, Haferlach C, Nowak D, Sato Y, Alpermann T, Nagasaki M, Shimamura T, Tanaka H, Chiba K, Yamamoto R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Nakamaki T, Ishiyama K, Nolte F, Hofmann WK, Miyawaki S, Chiba S, Mori H, Nakauchi H, Koeffler HP, Aburatani H, Haferlach T, Shirahige K, Miyano S, Ogawa S.
Nat Genet. 2013 Oct;45(10):1232-7. doi: 10.1038/ng.2731. Epub 2013 Aug 18.
PMID 23955599
Cohesin, a chromatin engagement ring.
Remeseiro S, Losada A.
Curr Opin Cell Biol. 2013 Feb;25(1):63-71. doi: 10.1016/ Epub 2012 Dec 6. (REVIEW)
PMID 23219370
Alteration of cohesin genes in myeloid diseases.
Rocquain J, Gelsi-Boyer V, Adelaide J, Murati A, Carbuccia N, Vey N, Birnbaum D, Mozziconacci MJ, Chaffanet M.
Am J Hematol. 2010 Sep;85(9):717-9. doi: 10.1002/ajh.21798.
PMID 20687102
Mutational inactivation of STAG2 causes aneuploidy in human cancer.
Solomon DA, Kim T, Diaz-Martinez LA, Fair J, Elkahloun AG, Harris BT, Toretsky JA, Rosenberg SA, Shukla N, Ladanyi M, Samuels Y, James CD, Yu H, Kim JS, Waldman T.
Science. 2011 Aug 19;333(6045):1039-43. doi: 10.1126/science.1203619.
PMID 21852505
Specific sites in the C terminus of CTCF interact with the SA2 subunit of the cohesin complex and are required for cohesin-dependent insulation activity.
Xiao T, Wallace J, Felsenfeld G.
Mol Cell Biol. 2011 Jun;31(11):2174-83. doi: 10.1128/MCB.05093-11. Epub 2011 Mar 28.
PMID 21444719


This paper should be referenced as such :
Chen, S ; Nagel, S ; Drexler, HG ; MacLeod, RAF
STAG2 (Stromal Antigen 2)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(4):272-275.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 6 ]
  Chronic Myelomonocytic Leukemia (CMML)
Myeloid proliferations in Down syndrome
t(X;7)(q25;p21) STAG2::BZW2
t(X;8)(q25;q22) VPS13B::STAG2
t(X;X)(q21;q25) STAG2::ATRX
t(X;X)(q25;q26) STAG2::GPR119

External links


HGNC (Hugo)STAG2   11355
LRG (Locus Reference Genomic)LRG_782
Atlas Explorer : (Salamanque)STAG2
Entrez_Gene (NCBI)STAG2    stromal antigen 2
AliasesHPE13; MKMS; NEDXCF; SA-2; 
SA2; SCC3B; bA517O1.1
GeneCards (Weizmann)STAG2
Ensembl hg19 (Hinxton)ENSG00000101972 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000101972 [Gene_View]  ENSG00000101972 [Sequence]  chrX:123961706-124102655 [Contig_View]  STAG2 [Vega]
ICGC DataPortalENSG00000101972
TCGA cBioPortalSTAG2
Genatlas (Paris)STAG2
SOURCE (Princeton)STAG2
Genetics Home Reference (NIH)STAG2
Genomic and cartography
GoldenPath hg38 (UCSC)STAG2  -     chrX:123961706-124102655 +  Xq25   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)STAG2  -     Xq25   [Description]    (hg19-Feb_2009)
GoldenPathSTAG2 - Xq25 [CytoView hg19]  STAG2 - Xq25 [CytoView hg38]
Genome Data Viewer NCBISTAG2 [Mapview hg19]  
OMIM300826   301022   301043   
Gene and transcription
Genbank (Entrez)AA428995 AK026678 AK098737 AK298633 AK313559
RefSeq transcript (Entrez)NM_001042749 NM_001042750 NM_001042751 NM_001282418 NM_001375366 NM_001375367 NM_001375368 NM_001375369 NM_001375370 NM_001375371 NM_001375372 NM_001375373 NM_001375374 NM_001375375 NM_001375376 NM_001375377 NM_006603
Consensus coding sequences : CCDS (NCBI)STAG2
Gene ExpressionSTAG2 [ NCBI-GEO ]   STAG2 [ EBI - ARRAY_EXPRESS ]   STAG2 [ SEEK ]   STAG2 [ MEM ]
Gene Expression Viewer (FireBrowse)STAG2 [ Firebrowse - Broad ]
GenevisibleExpression of STAG2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10735
GTEX Portal (Tissue expression)STAG2
Human Protein AtlasENSG00000101972-STAG2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8N3U4   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8N3U4  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8N3U4
Domaine pattern : Prosite (Expaxy)SCD (PS51425)   
Domains : Interpro (EBI)ARM-type_fold    Cohesin_Scc3/SA    SCD    STAG   
Domain families : Pfam (Sanger)STAG (PF08514)   
Domain families : Pfam (NCBI)pfam08514   
Conserved Domain (NCBI)STAG2
PDB (RSDB)4PJU    4PJW    4PK7    6QNX   
PDB Europe4PJU    4PJW    4PK7    6QNX   
PDB (PDBSum)4PJU    4PJW    4PK7    6QNX   
PDB (IMB)4PJU    4PJW    4PK7    6QNX   
Structural Biology KnowledgeBase4PJU    4PJW    4PK7    6QNX   
SCOP (Structural Classification of Proteins)4PJU    4PJW    4PK7    6QNX   
CATH (Classification of proteins structures)4PJU    4PJW    4PK7    6QNX   
AlphaFold pdb e-kbQ8N3U4   
Human Protein Atlas [tissue]ENSG00000101972-STAG2 [tissue]
Protein Interaction databases
IntAct (EBI)Q8N3U4
Ontologies - Pathways
Ontology : AmiGOchromosome, centromeric region  chromatin  chromatin  chromatin binding  protein binding  nucleus  nucleus  nucleoplasm  chromosome  cytosol  sister chromatid cohesion  sister chromatid cohesion  cohesin complex  cohesin complex  cohesin complex  membrane  nuclear matrix  nuclear meiotic cohesin complex  cell division  mitotic spindle assembly  mitotic spindle pole  
Ontology : EGO-EBIchromosome, centromeric region  chromatin  chromatin  chromatin binding  protein binding  nucleus  nucleus  nucleoplasm  chromosome  cytosol  sister chromatid cohesion  sister chromatid cohesion  cohesin complex  cohesin complex  cohesin complex  membrane  nuclear matrix  nuclear meiotic cohesin complex  cell division  mitotic spindle assembly  mitotic spindle pole  
REACTOMEQ8N3U4 [protein]
REACTOME PathwaysR-HSA-9018519 [pathway]   
NDEx NetworkSTAG2
Atlas of Cancer Signalling NetworkSTAG2
Wikipedia pathwaysSTAG2
Orthology - Evolution
GeneTree (enSembl)ENSG00000101972
Phylogenetic Trees/Animal Genes : TreeFamSTAG2
Homologs : HomoloGeneSTAG2
Homology/Alignments : Family Browser (UCSC)STAG2
Gene fusions - Rearrangements
Fusion : MitelmanSTAG2::C16orf45 [Xq25/16p13.11]  
Fusion Cancer (Beijing)cytochrome_b [STAG2]  -  Xq25 [FUSC000404]
Fusion : FusionHubAPEX2--STAG2    ARHGEF1--STAG2    ATP5A1--STAG2    ATRX--STAG2    CTSB--STAG2    CYTOCHROME_B--STAG2    EPHB1--STAG2    FER--STAG2    GLO1--STAG2    GPBP1--STAG2   
HIF1A--STAG2    HSPE1-MOB4--STAG2    IL1RAPL1--STAG2    LSM14A--STAG2    MYO1F--STAG2    OPHN1--STAG2    PAK3--STAG2    PTK2B--STAG2    RGL2--STAG2    RPL9--STAG2   
SART3--STAG2    STAG2--AMMECR1    STAG2--ANXA3    STAG2--C11ORF80    STAG2--C16ORF45    STAG2--CDK2AP1    STAG2--CIAPIN1    STAG2--CMC4    STAG2--CSTF2    STAG2--CT47A12   
Fusion : QuiverSTAG2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSTAG2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)STAG2
Exome Variant ServerSTAG2
GNOMAD BrowserENSG00000101972
Varsome BrowserSTAG2
ACMGSTAG2 variants
Genomic Variants (DGV)STAG2 [DGVbeta]
DECIPHERSTAG2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSTAG2 
ICGC Data PortalSTAG2 
TCGA Data PortalSTAG2 
Broad Tumor PortalSTAG2
OASIS PortalSTAG2 [ Somatic mutations - Copy number]
Cancer Gene: CensusSTAG2 
Somatic Mutations in Cancer : COSMICSTAG2  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DSTAG2
Mutations and Diseases : HGMDSTAG2
intOGen PortalSTAG2
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)STAG2
DoCM (Curated mutations)STAG2
CIViC (Clinical Interpretations of Variants in Cancer)STAG2
NCG (London)STAG2
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM300826    301022    301043   
Orphanet18904    27320    12485   
Genetic Testing Registry STAG2
NextProtQ8N3U4 [Medical]
Target ValidationSTAG2
Huge Navigator STAG2 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDSTAG2
Pharm GKB GenePA36177
Clinical trialSTAG2
DataMed IndexSTAG2
Other database
PubMed138 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Jan 20 14:18:17 CET 2022

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