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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
STAG1
STAG1 cohesin complex component
Chromosome 3 Β· 3q22.3
NCBI Gene: 10274Ensembl: ENSG00000118007.14HGNC: HGNC:11354UniProt: Q8WVM7
102PubMed Papers
21Diseases
0Drugs
54Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nucleoplasmnuclear bodynuclear matrixcohesin complexintellectual disability, autosomal dominant 47Intellectual disabilitygenetic disordercoronary artery disease
✦AI Summary

STAG1 is a core component of the cohesin complex that functions in sister chr3 cohesion and chr3 organization 1. The cohesin complex forms a proteinaceous ring structure that maintains chromosome 3 during cell division and regulates gene transcription through chr3 topology control 2. STAG1 works alongside its paralog STAG2, though they have distinct regulatory roles - while both proteins bind shared genomic loci, STAG2 occupies unique binding sites not compensated by STAG1 1. In hematopoietic stem cells, STAG1 and STAG2 display complementary but non-redundant functions in maintaining chr3 accessibility and controlling differentiation programs 2. Loss-of-function mutations in STAG1 cause intellectual developmental disorder, autosomal dominant 47, characterized by syndromic intellectual disability, distinctive facial features including wide mouth and deep-set eyes, and often epilepsy and microcephaly 34. The cohesinopathy phenotype results from disrupted gene regulation rather than solely chr3 segregation defects 3. STAG1 mutations are also implicated in cancer pathogenesis, with cohesin alterations occurring in up to 26% of cancer patients, highlighting its critical role in maintaining genomic stability and proper gene expression 5.

Sources cited
1
STAG1 is a cohesin complex component with distinct roles from STAG2 in chromatin regulation and hematopoietic cell function
PMID: 31495782
2
STAG1 and STAG2 have non-redundant functions in chromatin organization and gene regulation in hematopoietic cells
PMID: 39084219
3
STAG1 mutations cause intellectual developmental disorder with distinctive facial features, epilepsy, and microcephaly
PMID: 28119487
4
STAG1 variants expand the molecular spectrum of cohesinopathies causing neurodevelopmental disorders
PMID: 40625213
5
STAG mutations occur in up to 26% of cancer patients and are implicated in cancer pathogenesis
PMID: 31421907
Disease Associationsβ“˜21
intellectual disability, autosomal dominant 47Open Targets
0.81Strong
Intellectual disabilityOpen Targets
0.56Moderate
genetic disorderOpen Targets
0.51Moderate
coronary artery diseaseOpen Targets
0.46Moderate
stag1-related disorderOpen Targets
0.41Moderate
schizophreniaOpen Targets
0.41Moderate
complex neurodevelopmental disorderOpen Targets
0.37Weak
syndromic intellectual disabilityOpen Targets
0.37Weak
denturesOpen Targets
0.36Weak
rheumatoid arthritisOpen Targets
0.35Weak
atrial fibrillationOpen Targets
0.35Weak
Neurodevelopmental disorderOpen Targets
0.34Weak
intelligenceOpen Targets
0.33Weak
metabolic diseaseOpen Targets
0.32Weak
myocardial infarctionOpen Targets
0.32Weak
attention deficit hyperactivity disorderOpen Targets
0.31Weak
HypercholesterolemiaOpen Targets
0.31Weak
urinary bladder carcinomaOpen Targets
0.31Weak
major depressive disorderOpen Targets
0.30Weak
AnxietyOpen Targets
0.30Weak
Intellectual developmental disorder, autosomal dominant 47UniProt
Pathogenic Variants54
NM_005862.3(STAG1):c.1026+2T>CLikely pathogenic
not provided|Intellectual disability, autosomal dominant 47
β˜…β˜…β˜†β˜†2025
NM_005862.3(STAG1):c.1129C>T (p.Arg377Cys)Pathogenic
Intellectual disability, autosomal dominant 47|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 377
NM_005862.3(STAG1):c.1118G>A (p.Arg373Gln)Pathogenic
Intellectual disability, autosomal dominant 47|STAG1-related disorder|Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 373
NM_005862.3(STAG1):c.418C>T (p.Arg140Ter)Pathogenic
Intellectual disability, autosomal dominant 47
β˜…β˜…β˜†β˜†2022β†’ Residue 140
NM_005862.3(STAG1):c.1117C>T (p.Arg373Ter)Pathogenic
See cases|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 373
NM_005862.3(STAG1):c.1744-2A>GLikely pathogenic
Intellectual disability, autosomal dominant 47
β˜…β˜†β˜†β˜†2026
NM_005862.3(STAG1):c.2964C>A (p.Tyr988Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 988
NM_005862.3(STAG1):c.902G>A (p.Arg301His)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 301
NM_005862.3(STAG1):c.455_458del (p.Thr152fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 152
NM_005862.3(STAG1):c.3616C>T (p.Arg1206Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1206
NM_005862.3(STAG1):c.1141dup (p.Met381fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 381
NM_005862.3(STAG1):c.1339del (p.Ala447fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 447
NM_005862.3(STAG1):c.395-2A>TPathogenic
Intellectual disability, autosomal dominant 47
β˜…β˜†β˜†β˜†2025
NM_005862.3(STAG1):c.403del (p.Arg135fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 135
NM_005862.3(STAG1):c.1574_1575dup (p.Ile526fs)Likely pathogenic
Intellectual disability, autosomal dominant 47
β˜…β˜†β˜†β˜†2024β†’ Residue 526
NM_005862.3(STAG1):c.1433A>T (p.His478Leu)Likely pathogenic
Intellectual disability, autosomal dominant 47
β˜…β˜†β˜†β˜†2024β†’ Residue 478
NM_005862.3(STAG1):c.2911C>T (p.Arg971Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 971
NM_005862.3(STAG1):c.568C>T (p.Gln190Ter)Likely pathogenic
Intellectual disability, autosomal dominant 47
β˜…β˜†β˜†β˜†2024β†’ Residue 190
NM_005862.3(STAG1):c.282dup (p.Lys95fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 95
NM_005862.3(STAG1):c.1010G>A (p.Trp337Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2024β†’ Residue 337
View on ClinVar β†—
Related Genes
MDC1Protein interaction100%PDS5AProtein interaction100%TINF2Protein interaction100%WAPLProtein interaction100%SMC1BProtein interaction100%ESPL1Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
100%
Ovary
96%
Brain
89%
Lung
80%
Liver
39%
Gene Interaction Network
Click a node to explore
STAG1MDC1PDS5ATINF2WAPLSMC1BESPL1
PROTEIN STRUCTURE
Preparing viewer…
PDB6QB5 Β· 2.02 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.16Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.08 [0.05–0.16]
RankingsWhere STAG1 stands among ~20K protein-coding genes
  • #4,695of 20,598
    Most Researched102 Β· top quartile
  • #1,259of 5,498
    Most Pathogenic Variants54 Β· top quartile
  • #252of 17,882
    Most Constrained (LOEUF)0.16 Β· top 5%
Genes detectedSTAG1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation.
PMID: 31495782
Cell Stem Cell Β· 2019
1.00
2
PMID: 28119487
J Med Genet Β· 2017
0.90
3
STAG2 mutations reshape the cohesin-structured spatial chromatin architecture to drive gene regulation in acute myeloid leukemia.
PMID: 39084219
Cell Rep Β· 2024
0.80
4
Neurological Disease Syndrome Caused by a STAG1 Gene Variant: A Case Report and Literature Review.
PMID: 40625213
Int J Dev Neurosci Β· 2025
0.70
5
STAG Mutations in Cancer.
PMID: 31421907
Trends Cancer Β· 2019
0.60