GSX2
Chr 4ARGS homeobox 2
Also known as: DMJDS2, GSH2
GSX2 encodes a transcription factor that binds specific DNA sequences and regulates genes critical for brain development, particularly in specifying neuronal fates in the ventral telencephalon and striatal projection neurons. Autosomal recessive mutations cause diencephalic-mesencephalic junction dysplasia syndrome 2, a neurodevelopmental disorder affecting brain structures at the junction between the diencephalon and mesencephalon. This gene is essential for proper ventralization of brain progenitor cells and development of structures including the striatum and olfactory bulb interneurons.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
GSX2 · 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