SMN2

The SMN2 gene provides instructions for making a protein called SMN, which stands for "survival of motor neuron." The SMN protein is found throughout the body, with high levels in the spinal cord. This protein is particularly important for the survival of specialized nerve cells called motor neurons, which are located in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem). Healthy motor neurons are critical because they control muscle movements.

Several different versions of the SMN protein are produced from the SMN2 gene, but only one version (called isoform d) is full size and fully functional. The other versions are smaller and unstable. The full-size SMN protein made from the SMN2 gene is identical to the protein made from a similar gene called SMN1. A much smaller amount of full-size SMN protein is produced from the SMN2 gene compared with the SMN1 gene, however.

In cells, the SMN protein plays an important role in processing molecules called messenger RNA (mRNA), which serve as genetic blueprints for making proteins. Messenger RNA begins as a rough draft (pre-mRNA) and goes through several processing steps to a mature form. The SMN protein helps to assemble the cellular machinery needed to process pre-mRNA. The SMN protein may have additional functions in nerve cells. Research findings indicate that the SMN protein is important for the specialized outgrowths from nerve cells called dendrites and axons. Dendrites and axons are required for the transmission of impulses from nerve to nerve and from nerves to muscles.

amyotrophic lateral sclerosis - increased risk from variations of the SMN2 gene

A few studies suggest that a decreased number of SMN2 genes in each cell may be associated with an increased risk of developing amyotrophic lateral sclerosis. These studies found that people with amyotrophic lateral sclerosis were more likely to have only one copy of the SMN2 gene in each cell, instead of the usual two copies, compared with people unaffected by this disorder. Less SMN protein is produced as a result of the decreased number of SMN2 genes. A reduced amount of SMN protein might impair the function of motor neurons, which increases the risk of developing amyotrophic lateral sclerosis. The role of the SMN2 gene in this disorder is unclear, however, because other studies indicate that the number of SMN2 genes has no effect on the risk of developing amyotrophic lateral sclerosis.

spinal muscular atrophy - course of condition modified by extra copies of the SMN2 gene

Typically, people who do not have spinal muscular atrophy have two copies of the SMN1 gene and up to two copies of the SMN2 gene in each cell. In people affected by this disorder, both copies of the SMN1 gene are altered or missing. In some cases, particularly milder cases, affected individuals have three or more copies of the SMN2 gene. Among these individuals, additional copies of the SMN2 gene may modify the course of this disorder.

When both copies of the SMN1 gene are altered or missing, little or no SMN protein is produced from this gene. On a limited basis, the extra SMN2 genes can help compensate for this loss of SMN protein. Spinal muscular atrophy still occurs, however, because only a small amount of full-size SMN protein is produced from the SMN2 genes. In general, symptoms are less severe and begin later in life in affected individuals with three or more copies of the SMN2 gene compared to those with two copies of this gene.