EMX2

Chr 10

empty spiracles homeobox 2

NCBI Gene: 2018 ENSG00000170370 UniProt: Q04743

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a homeobox-containing transcription factor that is the homolog to the 'empty spiracles' gene in Drosophila. Research on this gene in humans has focused on its expression in three tissues: dorsal telencephalon, olfactory neuroepithelium, and urogenetial system. It is expressed in the dorsal telencephalon during development in a low rostral-lateral to high caudal-medial gradient and is proposed to pattern the neocortex into defined functional areas. It is also expressed in embryonic and adult olfactory neuroepithelia where it complexes with eukaryotic translation initiation factor 4E (eIF4E) and possibly regulates mRNA transport or translation. In the developing urogenital system, it is expressed in epithelial tissues and is negatively regulated by HOXA10. Alternative splicing results in multiple transcript variants encoding distinct proteins.[provided by RefSeq, Sep 2009]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSchizencephaly

Clinical highlights

Gene-disease validity (ClinGen)

schizencephaly · ADLimitednot for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.32

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

📖

GeneReview available — EMX2