Survival motor neuron 2 (SMN2) (SMN2)

Survival motor neuron 2 (SMN2) is a paralogous gene to SMN1, located on chromosome 5q13. In humans, SMN2 serves as a critical backup for SMN1, which is the primary producer of the survival motor neuron protein (UniProt P63162). In patients with spinal muscular atrophy (SMA), the SMN1 gene is deleted or mutated, making them entirely dependent on SMN2 for protein production (NCBI Gene: 6607). However, a C-to-T transition in exon 7 of SMN2 causes frequent exon skipping, leading to the production of a truncated, non-functional protein in approximately 90% of transcripts. The remaining 10% of full-length protein is insufficient to prevent the degeneration of alpha motor neurons in the spinal cord. Therapeutic strategies targeting SMN2 focus on modulating its pre-mRNA splicing to promote the inclusion of exon 7 (PMID: 28445658). Drugs like Nusinersen and Risdiplam bind to specific sequences in the SMN2 pre-mRNA to increase the levels of functional SMN protein (PMID: 30135318). This approach has revolutionized the treatment of SMA, transforming a once-fatal pediatric disease into a manageable condition.

Other names

SMNCSurvival of motor neuron 2, centromericBCD541GEMIN1Survival motor neuron protein 2

Splicing modulation to promote the inclusion of exon 7 in SMN2 pre-mRNA, thereby increasing the production of full-length, functional SMN protein.