Synaptic Ras GTPase-activating protein 1 pre-mRNA (SYNGAP1 pre-mRNA) (SYNGAP1 pre-mRNA)

Synaptic Ras GTPase-activating protein 1 (SYNGAP1) pre-mRNA is the primary transcript of the SYNGAP1 gene, which encodes a critical protein for synaptic development and plasticity (UniProt Q96PV0). The SYNGAP1 protein functions as a Ras GTPase-activating protein (GAP) at the postsynaptic density of excitatory neurons, where it negatively regulates Ras/Rap signaling to control dendritic spine maturation and synaptic strength (PubMed: 25074183). Mutations in one copy of the SYNGAP1 gene lead to haploinsufficiency, causing SYNGAP1-related intellectual disability, a condition characterized by cognitive impairment, early-onset epilepsy, and autism spectrum disorder (NIH: GeneReviews). SYNGAP1 pre-mRNA is a therapeutic target for antisense oligonucleotides (ASOs) like STK-002, which utilize splice-switching technology to increase the production of functional mRNA from the healthy allele (Stoke Therapeutics). By preventing the inclusion of non-productive exons or enhancing productive splicing, these therapies aim to restore SYNGAP1 protein levels and alleviate the neurological symptoms associated with the deficiency (PubMed: 31142833). This approach, known as Targeted Augmentation of Nuclear Gene Output (TANGO), represents a precision medicine strategy for addressing the root cause of haploinsufficiency-driven neurodevelopmental disorders. Clinical development of these RNA-targeted therapies involves monitoring seizure frequency and neurodevelopmental milestones as primary efficacy endpoints.

Other names

SYNGAP1 precursor messenger RNASynaptic Ras GAP 1 pre-mRNAMRD5 pre-mRNASYNGAP1 transcript

Antisense oligonucleotide-mediated splice modulation to increase productive mRNA levels (Targeted Augmentation of Nuclear Gene Output)