STAG1

Chr 3AD

STAG1 cohesin complex component

Also known as: MRD47, SA1, SCC3A

NCBI Gene: 10274 ENSG00000118007 UniProt: Q969W9 OMIM: 604358

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the SCC3 family and is expressed in the nucleus. It encodes a component of cohesin, a multisubunit protein complex that provides sister chromatid cohesion along the length of a chromosome from DNA replication through prophase and prometaphase, after which it is dissociated in preparation for segregation during anaphase. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.121 OMIM phenotype

Clinical Summary— STAG1

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

57 unique Pathogenic / Likely Pathogenic· 300 VUS of 698 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 7.69

OE 0.05 (0.03–0.12)

Highly constrained

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

Missense Constraint?

4.44Z-score

OE missense 0.51 (0.47–0.56)

338 obs / 658.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.05 (0.03–0.12)

0≤0.351.4

Missense OE?0.51 (0.47–0.56)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 4 / 76.7Missense obs/exp: 338 / 658.9Syn Z: -0.89

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSTAG1-related syndromic intellectual disabilityLOFAD

This gene — mechanism propensity

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 · 67% of P/LP variants are LoF · LOEUF 0.12 · ClinGen HI: Sufficient evidence for dosage pathogenicity

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.1

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

References

1.PMID 28119487 ↗

ClinVar Variant Classifications

698 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17

Likely Pathogenic40

VUS300

Likely Benign248

Benign36

Conflicting22

Pathogenic

Likely Pathogenic

300

VUS

248

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	1	2	0	17
Likely Pathogenic	24	15	1	0	40
VUS	5	270	21	4	300
Likely Benign	0	24	113	111	248
Benign	0	5	23	8	36
Conflicting	—				22
Total	43	315	160	123	663

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap STAG1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →