Loss of function of the zinc finger homeobox 4 gene, ZFHX4, underlies a neurodevelopmental disorder

ZFHX4 (truncating variants — LOF, haploinsufficiency)

LOF / haploinsufficiency + interactome study (histone modifications, trafficking, signal transduction, development)

Demonstration that ZFHX4 is a novel neurodevelopmental disorder gene via loss of function. Interactome analysis reveals roles in histone modifications, protein trafficking, signal transduction, and embryonic, neuronal and axonal development. ZFHX4 binds directly to promoters of key developmental genes.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

New gene to add to first-line NDD exome panels. Interaction evidence is consistent with a role as a transcriptional regulator of development — haploinsufficiency mechanism is coherent.

new NDD gene +3; de novo LOF +2; interactome analysis +2; small cohort +1; panel impact +1