Research
SON Gene Function in Neurodevelopment
Dr. Erin Eun-Young Ahn, Ph.D.
University of Alabama at Birmingham
Started January 2012
Funding
Ongoing basic research program; Dr. Ahn has studied SON since 2005
Investigating how loss-of-function variants in the SON gene disrupt RNA splicing in developing neurons, establishing the molecular basis for targeted therapeutic approaches to ZTTK syndrome.
Dr. Ahn's laboratory has been the world's leading center for SON gene research for over fifteen years. This foundational program established that SON protein is essential for nuclear speckle formation, pre-mRNA splicing of genes with weak splice sites, cell cycle regulation, and cilia formation — four critical cellular functions disrupted in ZTTK syndrome.
The SON protein acts as a core structural component of nuclear speckles alongside SRRM2, serving as a critical hub for RNA processing. When SON levels are reduced by half through haploinsufficiency, the resulting splicing defects cascade across hundreds of downstream genes essential for brain development and cellular metabolism.
In 2016, Dr. Ahn coordinated a collaboration of over 60 researchers that identified pathogenic SON mutations as the cause of ZTTK syndrome. Current work extends this foundation by mapping precisely which splicing events are most sensitive to SON dosage, identifying potential intervention points where therapeutic approaches could have the greatest impact.