What is the Difference Between SMN1 and SMN2 Gene?

The SMN1 and SMN2 genes are located within an inverted duplication on chromosome 5q13.2 and share more than 99% identity. These genes are responsible for producing survival motor neuron (SMN) protein, which is essential for the health and normal function of motor neurons. The main difference between SMN1 and SMN2 lies in a single nucleotide transition in exon 7 of SMN2.

Key differences between SMN1 and SMN2 include:

1. Disease gene: SMN1 is the disease gene because it produces the full-length SMN protein.
2. Disease-modifying gene: SMN2 is considered the disease-modifying gene due to the single nucleotide difference in exon 7.
3. SMN protein production: The SMN1 gene primarily produces the full-length form of SMN protein, while the SMN2 gene produces a smaller amount of the protein, with only 10% being fully functional.
4. Splicing patterns: The majority of the transcript from the SMN1 locus is full-length, whereas the majority of the transcript produced by the SMN2 locus lacks exon 7.

Spinal muscular atrophy (SMA) develops when there is a mutation in both copies of the SMN1 gene, leading to decreased production of SMN protein and resulting in motor neuron degeneration and muscle weakness. The severity of SMA is determined by the number of SMN2 genes a person has, with a higher copy number associated with less-severe symptoms.

Comparative Table: SMN1 vs SMN2 Gene

The SMN1 and SMN2 genes are part of the survival motor neuron (SMN) complex, which plays a crucial role in spinal muscular atrophy (SMA). The major difference between these two genes is a single nucleotide change (C-to-T transition) in exon 7 of SMN2, which disrupts an exonic splice enhancer and leads to the skipping of exon 7 in most SMN2 transcripts. Here is a table summarizing the differences between SMN1 and SMN2:

In SMA patients, the severity of the disease is inversely related to the copy number of SMN2. Type I SMA patients typically have deletions of SMN1 on both chromosomes, while type II and III SMA patients have various combinations of SMN1 and SMN2 deletions or conversions.