EOMES

Chr 3

eomesodermin

Also known as: TBR2

EOMES encodes a T-box transcription factor that is essential for early embryonic development, particularly mesoderm and endoderm specification during gastrulation, and for brain development including cerebral cortex intermediate progenitor cell specification and proliferation. Mutations cause microcephaly with intellectual disability and seizures with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.30
Clinical SummaryEOMES
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 91 VUS of 134 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.984
Z-score 4.17
OE 0.12 (0.050.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.86Z-score
OE missense 0.87 (0.790.96)
303 obs / 348.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.050.30)
00.351.4
Missense OE0.87 (0.790.96)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 3 / 25.9Missense obs/exp: 303 / 348.2Syn Z: -1.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedEOMES-related polymicrogyria and corpus callosum agenesisLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.3494th %ile
GOF
0.2696th %ile
LOF
0.86top 5%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

134 submitted variants in ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS91
Likely Benign16
Benign3
Conflicting2
16
Pathogenic
1
Likely Pathogenic
91
VUS
16
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
0
89
1
1
91
Likely Benign
0
5
1
10
16
Benign
0
2
0
1
3
Conflicting
2
Total0961912129

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

View in ClinVar →

Protein Context — Lollipop Plot

EOMES · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →