Cellular context defines brain-specific functions of genes associated with neurodevelopmental disorders

About 10% of ~1,000 neurodevelopmental disorder–associated genes show brain-preferential expression, while distinct clusters are upregulated in non-brain tissues with context-specific regulatory programs.

• Why it matters: Tissue-specific disease manifestations are not explained by differential expression alone, and NDD mechanisms remain poorly understood, motivating a way to quantify gene expression preferences across tissues and development.
• What they did: The authors built a computational framework integrating spatiotemporal transcriptome datasets to measure preferential expression across tissues and developmental stages, then analyzed regulatory mechanisms and protein-protein interaction partners.
• The result: They identify putative brain-specific interaction partners for 22 uniformly expressed NDD genes, experimentally validate QRICH1 interactions, and show disease-associated mutations disrupt them, supporting a molecular hypothesis for Ververi-Brady syndrome.