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…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 47MIM #617635

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · complex neurodevelopmental disorder · AD · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.12

LOEUF· LoF intol.

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in STAG1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

1,075 rare PASS variants

Rare truncating (LoF)

1 in 5,400

52 rare PASS variants

Rare synonymous (reference)

1 in 110

544 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for STAG1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 8,800
South Asian	~43k	1 in 66	1 in 1,400
Remaining (unassigned)	~30k	1 in 130	≈ 1 in 9,600
European (Finnish)	~27k	1 in 150	≈ 1 in 27,000
Admixed American	~22k	1 in 150	1 in 1,100
African / African American	~21k	1 in 100	≈ 1 in 6,300
East Asian	~20k	1 in 95	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 96	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.