SMN2 Gene: Function, Mutations, and Role in Spinal Muscular Atrophy

SMN2 (Survival of Motor Neuron 2, Centromeric) is a protein-coding gene located on chromosome 5q13.2. It is nearly identical to SMN1 but differs by a single nucleotide (c.840C>T) in exon 7, which disrupts an exonic splicing enhancer. This leads to predominant skipping of exon 7 during splicing, producing a truncated, unstable protein (SMNΔ7) that is rapidly degraded. Only about 10-20% of SMN2 transcripts produce full-length, functional SMN protein. SMN2 copy number varies in the human population and is the primary modifier of spinal muscular atrophy (SMA) severity: higher SMN2 copy numbers correlate with milder disease. SMN2 is a critical therapeutic target for SMA; drugs such as nusinersen (Spinraza) and risdiplam (Evrysdi) aim to increase SMN2 exon 7 inclusion and boost functional SMN levels.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• SMN complex assembly (Reactome: R-HSA-191859)

• Processing of capped intron-containing pre-mRNA (Reactome: R-HSA-72203)

• mRNA Splicing - Major Pathway (Reactome: R-HSA-72163)

The SMN2 gene encodes the survival motor neuron protein (SMN), a 294-amino acid protein (full-length isoform) that is nearly identical to the SMN1 product. The predominant SMN2 isoform (SMNΔ7) lacks exon 7, resulting in a truncated 282-amino acid protein that is unstable and rapidly degraded. Full-length SMN protein functions as part of the SMN complex, essential for the assembly of spliceosomal snRNPs and pre-mRNA splicing. SMN is ubiquitously expressed but is particularly critical for motor neuron survival. Reduced levels of functional SMN protein due to SMN1 loss and insufficient SMN2 compensation cause spinal muscular atrophy.