EMX2
Chr 10empty spiracles homeobox 2
The EMX2 protein is a homeobox transcription factor that patterns the developing neocortex into functional areas and regulates stereociliary bundle organization in the inner ear. Mutations cause schizencephaly, a rare brain malformation characterized by clefts extending from the brain surface to the ventricles, with inheritance typically following an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants (pLI 0.95), indicating that such mutations are likely to cause significant developmental abnormalities.
Limited evidence — not for standalone diagnostic reporting
Some data sources returned errors (1)
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
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
90 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 3 | 1 | 25 | 0 | 29 |
Likely Pathogenic | 0 | 1 | 3 | 0 | 4 |
VUS | 0 | 30 | 5 | 2 | 37 |
Likely Benign | 0 | 9 | 1 | 5 | 15 |
Benign | 0 | 0 | 1 | 1 | 2 |
Conflicting | — | 2 | |||
| Total | 3 | 41 | 35 | 8 | 89 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
EMX2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools