STAG2

Chr XXLDXLRX-linked

STAG2 cohesin complex component

Also known as: HPE13, MKMS, NEDXCF, SA-2, SA2, SCC3B, bA517O1.1

NCBI Gene: 10735ENSG00000101972UniProt: Q8N3U4

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]

Primary Disease Associations & Inheritance

Holoprosencephaly 13, X-linkedMIM #301043
XLDXLR
Mullegama-Klein-Martinez syndromeMIM #301022
X-linked
1
Active trials
25
Pathogenic / LP
248
ClinVar variants
63
Pubs (1 yr)
4.9
Missense Z· constrained
0.09
LOEUF· LoF intolerant
Clinical Summary— STAG2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 130 VUS of 248 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — STAG2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.09LOEUF
pLI 1.000
Z-score 6.61
OE 0.02 (0.01–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
4.94Z-score
OE missense 0.34 (0.30–0.39)
151 obs / 443.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.01–0.09)
0≤0.351.4
Missense OE0.34 (0.30–0.39)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 1 / 52.8Missense obs/exp: 151 / 443.7Syn Z: -0.37
LOF
DN
0.2299th %ile
GOF
0.2995th %ile
LOF
0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 32% of P/LP variants are LoF · LOEUF 0.09

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

248 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic6
VUS130
Likely Benign84
Benign8
Conflicting1
19
Pathogenic
6
Likely Pathogenic
130
VUS
84
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
13
0
19
Likely Pathogenic
2
2
2
0
6
VUS
1
116
12
1
130
Likely Benign
0
3
42
39
84
Benign
0
0
6
2
8
Conflicting
—1
Total91217542248

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

STAG2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

STAG2-related developmental delay with microcephaly and congenital anomalies

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A novel NMD-escaping STAG2 variant associated with syndromic neurodevelopmental delay, growth failure, and distinctive dysmorphism: expanding the phenotype in male patients and literature review.
Ahmad F et al.·Gene
2026Review
Tumor-suppressive activities of SA1/STAG2 and effects of PARP impairment during brain development.
Totaro S et al.·Dis Model Mech
2026Open Access
Novel variants in STAG2 and PKD1 associate with multiple congenital malformations and autosomal dominant polycystic kidney disease in a Chinese family: A case report and literature review.
Yang Q et al.·Exp Ther Med
2026Open AccessReview
STAG2-truncating variants reveal a mosaic STAG2 inactivation pattern and compensatory mechanisms involving cohesin complex remodeling.
Moronta Gines M et al.·iScience
2025Open AccessFunctional
A Novel STAG2 Frameshift Variant in Mullegama-Klein-Martinez Syndrome with Complex Conotruncal Heart Defect.
Wang H.·Genes (Basel)
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients