NEFH

The NEFH gene provides instructions for making a protein component (subunit) of neurofilaments. Neurofilaments make up a structural framework that helps to define the shape and size of nerve cells (neurons). Neurofilaments are assembled from light, medium, and heavy subunits. The heavy subunit is produced from the NEFH gene.

Neurofilaments cross-link with one other, forming bridges that help maintain the diameter of the fiber, or axon, that extends from a neuron. Maintaining a proper axon diameter is important for the transmission of nerve impulses. Neurofilaments are particularly abundant in motor neurons, which are specialized nerve cells in the brain and spinal cord that control muscle movement.

The heavy subunit is made up of three regions: the head, which regulates assembly of neurofilaments; a coiled midsection; and a tail with branches that interact with other proteins (including other neurofilaments). The tail region has a segment called the KSP motif that plays an important role in regulating the functions of neurofilaments.

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

Mutations in the NEFH gene increase the chances of developing amyotrophic lateral sclerosis (ALS), a condition characterized by progressive movement problems and muscle wasting. Most of these mutations delete or insert DNA building blocks (nucleotides) in the NEFH gene, which produces a KSP motif that is shorter or longer than normal. The abnormal KSP motif may disrupt cross-linking between neurofilaments. One NEFH gene mutation that can lead to ALS changes a single protein building block (amino acid) used to make the heavy subunit. The effect of this mutation is unknown, but it may impair the assembly of neurofilaments.

It is not known how NEFH gene mutations raise the risk of developing ALS. Disrupted cross-linking or impaired assembly of neurofilaments may lead to the accumulation of these filaments in motor neurons. A buildup of neurofilaments in deteriorating motor neurons appears to be an early feature of ALS. It is unclear, however, whether these deposits play a role in causing this disorder or are a byproduct of dying motor neurons.