Senior Researcher Pekka Postila from the University of Turku and InFLAMES Flagship has been awarded  €120,000 Investigator Award from the California-based SynGAP Research Fund to investigate the effects of missense mutations on the SynGAP1 protein. Additionally, Doctoral Researcher Aliaa E. Ali has received full two-year PhD funding from the Finnish Cultural Foundation for her work on SynGAP1 modeling.

SynGAP1 is a crucial protein in neuronal development. Mutations in the SynGAP1 gene lead to Non-Syndromic Intellectual Disability (NSID), with an estimated incidence of 6 per 100,000 people. Symptoms of SynGAP1-related NSID include epilepsy, autism, hypotonia, and intellectual disability, which typically manifest in early childhood. Diagnosing the condition is challenging due to the diverse range of symptoms. Despite its rarity, NSID may account for 2–8% of all intellectual disabilities globally. SynGAP1 has also been linked to Alzheimer’s disease, tumor formation, and other developmental disorders.

Most SynGAP1-related NSID cases likely result from missense mutations, where one amino acid in the protein is replaced by another. These mutations are difficult to annotate due to the lack of structural data supporting the diagnostic process.

To address this, SynGAP1 modeling research has focused on using computational structure-based methods to support the diagnosis of SynGAP1 missense variants. The research led by Docent Postila aims to shed light on the key macromolecular interactions of SynGAP1 in the postsynaptic density and the potential of missense mutations to disrupt these interactions in disease states.

“We are deeply honored by the continued confidence and support of the SynGAP Research Fund for our modeling research on SynGAP. We are also very pleased that Aliaa has received the grant from the Finnish Cultural Foundation. As researchers, we believe it is morally imperative to tackle SynGAP-related neurodevelopmental disorders, as they primarily affect the most vulnerable members of our society—children,” says Pekka Postila.

The research is conducted in close collaboration with Drs Michael J. Courtney and Li-Li Li at the Neural Signalling Laboratory of the Turku Bioscience Centre, and Dr Jukka V. Lehtonen at the Structural Bioinformatics Laboratory of Åbo Akademi University.

Since 2020, the University of Turku has received a total of nine grants for SynGAP1 research, amounting to over €1.3 million in funding.