STAG1

Chr 3AD

STAG1 cohesin complex component

Also known as: MRD47, SA1, SCC3A

Encodes a component of the cohesin complex that maintains sister chromatid cohesion during cell division. Mutations cause autosomal dominant intellectual developmental disorder with onset in early childhood. The gene is highly constrained against loss-of-function variants, indicating that such variants are likely pathogenic when they occur.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 47MIM #617635
AD
1
Active trials
20
Pubs (1 yr)
18
P/LP submissions
11%
P/LP missense
0.12
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical SummarySTAG1
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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.
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ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 151 VUS of 300 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 7.69
OE 0.05 (0.030.12)
Highly constrained

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

Missense Constraint
4.44Z-score
OE missense 0.51 (0.470.56)
338 obs / 658.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.05 (0.030.12)
00.351.4
Missense OE0.51 (0.470.56)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 4 / 76.7Missense obs/exp: 338 / 658.9Syn Z: -0.89
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSTAG1-related syndromic intellectual disabilityLOFAD
DN
0.3196th %ile
GOF
0.4085th %ile
LOF
0.69top 10%

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

LOFprediction above median · 1 literature citation · 44% of P/LP variants are LoF · LOEUF 0.12

Literature Evidence

LOFFunctional studies of the variants and studies of patient cells were not performed, but Lehalle et al. (2017) postulated that the neurodevelopmental phenotype is caused by STAG1 haploinsufficiency with a putative disruptive effect on transcriptional regulation.PMID:28119487

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

300 submitted variants in ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic6
VUS151
Likely Benign91
Benign3
Conflicting3
12
Pathogenic
6
Likely Pathogenic
151
VUS
91
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
7
0
12
Likely Pathogenic
3
2
1
0
6
VUS
3
134
11
3
151
Likely Benign
0
5
44
42
91
Benign
0
1
2
0
3
Conflicting
3
Total111426545266

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

View in ClinVar →

Protein Context — Lollipop Plot

STAG1 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC