SH3 and multiple ankyrin repeat domains protein 3 messenger RNA (SHANK3 mRNA)

SH3 and multiple ankyrin repeat domains protein 3 (SHANK3) messenger RNA (mRNA) is a critical target for genetic therapies addressing neurodevelopmental disorders. The SHANK3 protein encoded by this transcript acts as a primary scaffold in the postsynaptic density of excitatory synapses, organizing receptors and signaling molecules (UniProt Q9BYB0). Mutations or deletions in the SHANK3 gene lead to haploinsufficiency, which is the underlying cause of Phelan-McDermid syndrome and a significant subset of autism spectrum disorder cases (OMIM 606232). Because the disease is often caused by having only one functional copy of the gene, therapeutic strategies focus on increasing the output of the remaining SHANK3 mRNA. Investigational approaches include antisense oligonucleotides (ASOs) designed to upregulate protein expression by targeting regulatory elements or natural antisense transcripts (PMID: 32814900). These RNA-targeted therapies aim to restore synaptic connectivity and improve cognitive and motor functions in affected individuals. Preclinical models have shown that restoring SHANK3 levels can reverse many of the physiological and behavioral symptoms associated with its deficiency. However, drug development faces challenges such as ensuring efficient delivery across the blood-brain barrier and avoiding the toxic effects of SHANK3 overexpression (PMID: 28190781). Monitoring efficacy typically involves measuring protein levels in the central nervous system or observing changes in electroencephalogram (EEG) patterns. Overall, SHANK3 mRNA represents a high-value target for precision medicine in neuropsychiatry.

Other names

ProSAP2 mRNAPSAP2 mRNASCZD15 mRNA22q13.3 deletion syndrome gene transcript

Upregulation of protein expression through RNA-targeted modulation