The survival motor neuron 1 (SMN1) gene encodes the survival motor neuron (SMN) protein, a ubiquitously expressed protein that is especially critical for the maintenance and function of spinal motor neurons.
Pathogenic variants or deletions in both copies of SMN1 are the principal cause of autosomal recessive spinal muscular atrophy (SMA), a leading genetic cause of infant mortality.
SMN1 gene is located on chromosome 5q13 and produces the full-length SMN protein that forms part of the SMN complex, which is involved in small nuclear ribonucleoprotein (snRNP) assembly and pre‑mRNA splicing.
SMN protein is present throughout the body but is most abundant in the spinal cord, where it supports survival and function of alpha motor neurons and proper axonal and dendritic architecture.
Humans also carry a closely related paralog, SMN2, which differs from SMN1 by a few nucleotides, notably a C>T change in exon 7 that promotes exon 7 skipping.
In more than 95% of patients with typical 5q‑SMA, there is a homozygous deletion or conversion of SMN1, while the remaining cases harbor intragenic SMN1 mutations.
Reduced SMN levels lead to widespread splicing defects and impaired RNA metabolism in motor neurons, ultimately causing progressive motor neuron degeneration, muscle weakness, and atrophy that define SMA.
SMA due to SMN1 is inherited in an autosomal recessive pattern: affected individuals usually have biallelic loss or mutation of SMN1, while carriers have one functional and one nonfunctional copy.
Disease-modifying treatments for SMA, including antisense oligonucleotides that modulate SMN2 splicing and gene replacement therapy delivering a functional SMN1 cDNA via AAV9, are specifically designed to increase SMN protein levels in motor neurons.
Early identification of SMN1 loss through newborn screening enables timely initiation of these therapies, which markedly improves survival and motor outcomes compared with historical cohorts.