Survival motor neuron 1 (SMN1) (SMN1)

Survival motor neuron 1 (SMN1) is a gene located on chromosome 5q that encodes the SMN protein, a ubiquitous protein essential for the survival of motor neurons (UniProt P63162). The SMN protein is a key component of the SMN complex, which facilitates the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome responsible for pre-mRNA splicing (NCBI Gene ID: 6606). Homozygous loss or mutation of SMN1 results in Spinal Muscular Atrophy (SMA), a devastating neuromuscular disorder characterized by the progressive degeneration of alpha motor neurons in the spinal cord, leading to muscle weakness and respiratory failure (PubMed: 31535351). While the nearly identical SMN2 gene exists, it cannot fully compensate for the loss of SMN1 because a single nucleotide change causes the exclusion of exon 7 in most transcripts, resulting in a truncated and unstable protein (PubMed: 29431111). Therapeutic intervention via AAV-hSMN1 transgene delivery, such as onasemnogene abeparvovec, utilizes an adeno-associated virus vector to deliver a functional copy of the human SMN1 gene directly into the nuclei of target cells (FDA: Zolgensma Label). This gene replacement therapy restores the production of full-length SMN protein, addressing the underlying genetic deficiency and significantly improving motor milestones and survival in patients with SMA (PubMed: 29106850).

Other names

SMNSMA1SMA2SMA3SMA4GEMIN1Survival of motor neuron 1, telomericT-SMN

Gene replacement therapy involving the delivery of a functional human SMN1 cDNA sequence using a non-replicating adeno-associated virus serotype 9 (AAV9) vector to restore SMN protein expression in motor neurons (FDA: Zolgensma Label).