STAG2
protein-codingstromal antigen 2, the group of Cohesin complex|Armadillo like helical domain containing
Gene summary
The protein encoded by this gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Targeted inactivation of this gene results in chromatid cohesion defects and aneuploidy, suggesting that genetic disruption of cohesin is a cause of aneuploidy in human cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~462.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0026722
Submitter: G2P
Inheritance Pattern: XL
Disease ID:MONDO:0026722
Submitter: PanelApp Australia
Inheritance Pattern: XL
Disease ID:MONDO:0026722
Submitter: Illumina
Inheritance Pattern: XL
Disease ID:MONDO:0026722
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: XL
Disease ID:MONDO:0010507
Submitter: Ambry Genetics
Inheritance Pattern: XL
Disease ID:MONDO:0026722
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Craniofacial; Musculoskeletal; Neurologic
Intervention: Cardiovascular
Rationale: The conditions can involve congenital cardiac anomalies, and awareness may allow early management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to STAG2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001042750.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 51 | 134 | 14 | 199 | ||
| missense | 2 | 10 | 432 | 17 | 5 | 466 |
| nonsense | 8 | 6 | 22 | 36 | ||
| start loss | 0 | |||||
| frameshift | 8 | 5 | 4 | 17 | ||
| splice donor/acceptor (+/-2bp) | 6 | 7 | 75 | 88 | ||
| Total | 24 | 28 | 584 | 151 | 19 | 806 |
Highest pathogenic variant AF is 9.1267856e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001036215.1 | 33 | MANE Select | |
| Ensembl | ENSP00000360187.4 | 33 | MANE Select | |
| RefSeq | NP_001036214.1 | 33 | Standard | |
| RefSeq | NP_001036216.1 | 32 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell cycle - Homo sapiens (human)
- Signal Transduction
- SUMOylation of DNA damage response and repair proteins
- Post-translational protein modification
- SUMO E3 ligases SUMOylate target proteins
Biological Process
- sister chromatid cohesion
- negative regulation of DNA endoreduplication
- cell division
- meiotic cell cycle
- regulation of mitotic spindle assembly
Molecular Function
- chromatin binding
- protein binding
Cellular Component
- chromosome, centromeric region
- chromatin
- nucleus
- nucleoplasm
- chromosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000218089
- Coding exons
- 33
- Length
- 462453
- Individuals with no LoFs
- 121668
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 121669
- p
- 0.00000411
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.94 | 151 | 444 | 0.340 | 0.0000324 | 8460 |
| Missense (PolyPhen) | 20 | 132.2 | 0.15128 | 2573 | ||
| Synonymous | -0.369 | 146 | 140 | 1.04 | 0.00000971 | 2208 |
| Loss of Function | 6.61 | 1 | 52.8 | 0.0189 | 0.00000432 | 926 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000063 | 0.000047 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. {ECO:0000269|PubMed:12034751}.;
Intolerance Scores
- RVIS EVS
- -0.63
- RVIS percentile EVS
- 17.03
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.894
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |