Syntaxin-binding protein 1 mRNA (STXBP1 mRNA)

Syntaxin-binding protein 1 (STXBP1) mRNA encodes the Munc18-1 protein, which is essential for the docking and fusion of synaptic vesicles with the presynaptic membrane (UniProt: P61764; NCBI Gene: 6812). Munc18-1 acts as a molecular chaperone for syntaxin-1A, facilitating the assembly of the SNARE complex required for neurotransmitter release (PubMed: 30333164). Mutations in the STXBP1 gene, typically resulting in haploinsufficiency, are a primary cause of STXBP1-related encephalopathy, a severe neurodevelopmental disorder characterized by early-onset epilepsy and global developmental delay (PubMed: 32814901). Because the disease is often caused by having only one functional copy of the gene, the mRNA is a high-priority therapeutic target for genetic medicines (Stoke Therapeutics). Current drug development efforts focus on using antisense oligonucleotides (ASOs) to modulate mRNA splicing or stability to increase the production of functional Munc18-1 protein from the remaining healthy allele (Stoke Therapeutics; PubMed: 32814901). These RNA-targeted therapies, such as those utilizing TANGO technology, aim to restore normal synaptic function and alleviate the neurological symptoms associated with the deficiency (Stoke Therapeutics).

Other names

MUNC18-1 mRNARBSEC1 mRNAUNC18A mRNAN-Sec1 mRNAhUNC18 mRNA

Targeted Augmentation of Nuclear Gene Output (TANGO) via antisense oligonucleotides to increase functional protein expression (Stoke Therapeutics; PubMed: 32814901).