SynGAP Research Fund awards $100,000 for investigating the impact of SYNGAP1 missense variants using structural bioinformatics

TURKU, Finland – October 27, 2023 – The SynGAP Research Fund 501(c)(3) announced a $100,000 grant to researchers Pekka Postila and Olli Pentikäinen from the Institute of Biomedicine and InFLAMES Flagship at the University of Turku. Prof. Pentikäinen’s research focuses on molecular modeling and computer-aided drug discovery. Assoc. Prof. Postila is an expert on advanced molecular dynamics simulations of complex biomolecular systems. The dual research team was formed to study the structural effects of missense variants on the SynGAP protein, whose normal functioning is vital for neuronal development. 

Missense variants are genetic alterations that change a single amino acid in a protein. Such changes can cause SynGAP-related disorders, but they are challenging to interpret and, thus, they are under-diagnosed. This research aims to solve this problem by 

1) studying how missense variants affect SynGAP structure and its interactions;
2) evaluating the contribution of sequence and structural variation in SynGAP to disease status and severity o; and
3) developing the online portal known as SGM server for centralizing and exploring all identified SYNGAP1 missense variants, including the variants of unknown significance.

The SGM server is intended to assist in diagnosing SynGAP-related disorders caused by missense variants. It combines sequence-based and machine learning-based methods to analyze missense variants in the SynGAP protein. It also provides structural annotation and visualization of the variants using a 3D viewer. This allows users to easily explore the effects of missense mutations in one platform. “Having all the relevant data, including the variant structures, in one place will make it easier to assess the impact of missense mutations.” says Prof. Postila. 

“We are thrilled to see SYNGAP1 research grow at Turku with this work.  The collaboration with Dr. Courtney’s ongoing SRF-supported SYNGAP1 research is the kind of collaboration we seek to foster.” says Katrein Deckers, Chair of Syngap Research Fund Europe.

Michael Graglia, Managing Director at SRF USA, states “This work is essential.  A key driver of SYNGAP1 underdiagnosis is missense mutations being classified as variants of uncertain significance (VUS).  Making an open source tool like this will both accelerate the science of SYNGAP1 and support clinicians working to resolve SYNGAP1 VUS for their patients.”

Prof. Pentikäinen also expresses faith in that “By combining structural bioinformatics, molecular dynamics simulations, and available SynGAP variant data, it is possible to reveal the role of missense variants on the protein’s function and to potentially identify new pathogenic variants as well.”   

 Dr. Michael Courtney & Assoc. Prof. Postila will both present updates on their work at the upcoming SYNGAP1 Conference 2023: Uniting for Progress in Orlando, Florida on November 30th, 2023.  Researchers and clinicians are encouraged to register and join for a full day of updates on the rapidly expanding field of SYNGAP1 science and medicine.

‍About Institute of Biomedicine and InFLAMES Flagship  

The Institute of Biomedicine at the University of Turku is a research and education unit that focuses on biomedical sciences. The institute has three main research areas: infection and immunity, integrative physiology and pharmacology, and cancer research. The institute also offers bachelor’s and master’s degree programmes in biomedicine, drug discovery and development, and biomedical imaging. The institute collaborates with local and international partners to advance the understanding and treatment of human diseases 

InFLAMES Research Flagship is an innovation ecosystem based on the immune system. It is a joint effort of University of Turku, Åbo Akademi University and the associated ecosystem in Turku, Finland. It is supported by the Research Council of Finland. We are an internationally recognized, top-level, immunological research and development cluster attracting both researchers and business partners. Our goals are to enhance entrepreneurship and the translation of new inventions, develop and exploit new diagnostic and therapeutic tools for personalized medicine and boost public-private companionship.  

About SYNGAP1-related intellectual disability (SRID)

SYNGAP1-related intellectual disability (ICD-10 F78.A1) is a rare genetic disorder caused by variants on the SYNGAP1 gene that reduce SynGAP protein levels. SRF has identified almost over 1,300 patients to date, the number grows weekly.  This protein acts as a regulator in the synapses (where neurons communicate with each other). When SynGAP protein levels are too low, we see an increase in excitability in the synapses making it difficult for neurons to communicate effectively. This leads to many neurological issues seen in SynGAP patients.

Symptoms of SYNGAP1 include: intellectual disability; epilepsy; hypotonia (low muscle tone); gross and fine motor skill delays; autism spectrum disorder; gastro-intestinal disorders; sleep and behavior disorders and visual abnormalities. 

About the SynGAP Research Fund (SRF)

The mission of the SynGAP Research Fund (SRF) is to improve the quality of life for SYNGAP1 patients through the research and development of treatments, therapies and support systems. 

SRF was founded in the US in 2018 as a 501(c)(3) US public charity, and families created sister organizations for SRF in the UK in 2020, in Europe (Netherlands) in 2022, and in Latin America (Colombia) in 2023. 

Completely parent-led, SRF is the largest non-government funder of SynGAP research having committed over $4 million in grants to date. The founders cover all operational costs, ensuring donations fund science. SRF’s grant program awards one or two-year grants to investigators, physician residents, and clinicians who are interested in studying SYNGAP1. SRF grants are intended to help researchers explore novel ideas and answer open questions related to the clinical aspects of and therapies for SRID. 

SRF is a member of the COMBINEDbrain, Global Genes Foundation Alliance, the Everylife Foundation Community Congress, Personalized Medicine Coalition, Rare Epilepsy Network, and the Epilepsy Leadership Council.

For more on SRF, visit: SyngapResearchFund.org or follow @cureSYNGAP1 on Twitter, LinkedIn, YouTube, Instagram, Facebook or TikTok.

‍Mike announced the grant in Episode 121 of the SYNGAP1 Podcast, SYNGAP10, also available on Youtube.