STAG3

Chr 7AR

STAG3 cohesin complex component

Also known as: SA3, SPGF61

NCBI Gene: 10734ENSG00000066923UniProt: Q9UJ98

The protein encoded by this gene is expressed in the nucleus and is a subunit of the cohesin complex which regulates the cohesion of sister chromatids during cell division. A mutation in this gene is associated with premature ovarian failure. Alternate splicing results in multiple transcript variants encoding distinct isoforms. This gene has multiple pseudogenes. [provided by RefSeq, Apr 2014]

Primary Disease Associations & Inheritance

Premature ovarian failure 8MIM #615723
AR
Spermatogenic failure 61MIM #619672
AR
63
ClinVar variants
2
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— STAG3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
2 Pathogenic / Likely Pathogenic· 57 VUS of 63 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.61LOEUF
pLI 0.000
Z-score 4.32
OE 0.45 (0.34–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.66Z-score
OE missense 0.82 (0.77–0.88)
569 obs / 691.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.45 (0.34–0.61)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.77–0.88)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 33 / 72.8Missense obs/exp: 569 / 691.7Syn Z: 1.08

ClinVar Variant Classifications

63 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic1
VUS57
Likely Benign4
1
Pathogenic
1
Likely Pathogenic
57
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
1
0
0
0
1
VUS
1
56
0
0
57
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total2601063

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

View in ClinVar →

Protein Context — Lollipop Plot

STAG3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
STROMAL ANTIGEN 3; STAG3
MIM #608489 · *

Premature ovarian failure 8

MIM #615723

Molecular basis of disorder known

Autosomal recessive

Spermatogenic failure 61

MIM #619672

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Novel STAG3 variant associated with primary ovarian insufficiency and non-obstructive azoospermia in an Iranian consanguineous family.
Akbari A et al.·Gene
2022
Novel STAG3 variant causes oligoasthenoteratozoospermia with high sperm aneuploidy rate.
Tsabai PN et al.·J Assist Reprod Genet
2025Case report
STAG3 homozygous missense variant causes primary ovarian insufficiency and male non-obstructive azoospermia.
Jaillard S et al.·Mol Hum Reprod
2020Case report
New STAG3 gene variant as a cause of premature ovarian insufficiency.
Gómez-Rojas S et al.·Rev Colomb Obstet Ginecol
2022
A Long Contiguous Stretch of Homozygosity Disclosed a Novel STAG3 Biallelic Pathogenic Variant Causing Primary Ovarian Insufficiency: A Case Report and Review of the Literature.
Mellone S et al.·Genes (Basel)
2021Review
STAG3 truncating variant as the cause of primary ovarian insufficiency.
Le Quesne Stabej P et al.·Eur J Hum Genet
2016
Meiosis interrupted: the genetics of female infertility via meiotic failure.
Biswas L et al.·Reproduction
2021Review
Evaluation of the Stag3 gene and the synaptonemal complex in a rat model (as/as) for male infertility.
Bayés M et al.·Mol Reprod Dev
2001Functional
Mutations in the stromal antigen 3 (STAG3) gene cause male infertility due to meiotic arrest.
van der Bijl N et al.·Hum Reprod
2019
Genetics of ovulatory dysfunction and infertility: a scoping review and gene ontology analysis.
DiPietro EE et al.·Front Endocrinol (Lausanne)
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools