STAG3

Chr 7AR

STAG3 cohesin complex component

Also known as: SA3, SPGF61

NCBI Gene: 10734 ENSG00000066923 UniProt: Q9UJ98 OMIM: 608489

The protein is a meiosis-specific component of the cohesin complex that maintains sister chromatid cohesion during cell division by forming a proteinaceous ring that traps sister chromatids until anaphase. Mutations cause premature ovarian failure and male spermatogenic failure, reflecting the protein's essential role in meiotic chromosome segregation in germ cells. The condition follows autosomal recessive inheritance and primarily affects reproductive function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.612 OMIM phenotypes

Clinical Summary— STAG3

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

27 unique Pathogenic / Likely Pathogenic· 148 VUS of 278 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.61LOEUF

pLI 0.000

Z-score 4.32

OE 0.45 (0.34–0.61)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.66Z-score

OE missense 0.82 (0.77–0.88)

569 obs / 691.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.34–0.61)

0≤0.351.4

Missense OE?0.82 (0.77–0.88)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 33 / 72.8Missense obs/exp: 569 / 691.7Syn Z: 1.08

This gene — mechanism propensity

0.6646th %ile

GOF

0.5464th %ile

LOF

0.2969th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

278 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12

Likely Pathogenic15

VUS148

Likely Benign30

Benign35

Conflicting1

Pathogenic

Likely Pathogenic

148

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	0	1	0	12
Likely Pathogenic	12	3	0	0	15
VUS	1	146	0	1	148
Likely Benign	0	13	3	14	30
Benign	0	2	31	2	35
Conflicting	—				1
Total	24	164	35	17	241

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap STAG3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →