SMN1

SMN1, or survival motor neuron 1, is a human gene located on chromosome 5q13. It encodes the survival motor neuron protein, a component of the SMN complex essential for the biogenesis of small nuclear ribonucleoproteins (snRNPs) involved in pre-mRNA splicing. In humans, SMN1 has a close paralog, SMN2, which differs by a few nucleotides, most notably a C to T transition in exon 7 that alters splicing.

SMN1 operates in the cytoplasm and nucleus as part of the SMN complex, cooperating with Gemin proteins to assemble snRNPs, a step required for proper splicing of many transcripts. Adequate SMN protein levels are particularly important for motor neurons, but the exact reasons for selective vulnerability remain under study.

Genetically, loss or mutation of SMN1 on both chromosome 5 copies causes spinal muscular atrophy (SMA), a neurodegenerative disorder characterized by progressive weakness and atrophy of skeletal muscles due to motor neuron loss. The SMN2 gene modifies disease severity because it can partially compensate by producing some full-length SMN protein, despite predominantly generating a truncated, less functional form. The total SMN protein available is influenced by SMN2 copy number, with more copies generally associated with milder SMA phenotypes.

Diagnosis typically involves genetic testing for SMN1 deletions or mutations, with SMN2 copy number considered for prognosis. Treatments approved for SMA aim to increase functional SMN protein levels: nusinersen (Spinraza) promotes inclusion of exon 7 in SMN2 transcripts; risdiplam (Evrysdi) modulates SMN2 splicing; and gene therapy with onasemnogene abeparvovec (Zolgensma) delivers functional SMN1. Ongoing research seeks to improve therapies and understand SMN1/SMN2 biology further.