Reviewed August 2007
What is the official name of the NEFH gene?
The official name of this gene is “neurofilament, heavy polypeptide 200kDa.”
NEFH is the gene's official symbol. The NEFH gene is also known by other names, listed below.
What is the normal function of the NEFH gene?
The NEFH gene provides instructions for making a protein component (subunit) of neurofilaments, which are essential for the structure of nerve cells. Neurofilaments are assembled from three different protein subunits called light, medium, and heavy. The heavy subunit is produced from the NEFH gene.
Neurofilaments form a structural framework that helps to define the shape and size of nerve cells. Cross-linking or bridging between neurofilaments maintains the diameter of nerve cells, which is important for the conduction 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.
How are changes in the NEFH gene related to health conditions?
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amyotrophic lateral sclerosis - increased risk from variations of the NEFH gene
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Mutations in the NEFH gene have been detected in a small percentage of individuals with amyotrophic lateral sclerosis. In some cases, unaffected family members of people with this disorder also have a NEFH mutation. Based on these observations, a mutation in the NEFH gene appears to increase the risk of developing amyotrophic lateral sclerosis but does not directly cause this disorder.
Researchers have identified several mutations that delete or insert DNA building blocks (base pairs) within the NEFH gene, which produces a KSP motif of abnormal length. The abnormal KSP motif may disrupt cross-linking between neurofilaments. One NEFH mutation changes one of the protein building blocks (amino acids) used to make the heavy subunit. Specifically, the amino acid alanine replaces the amino acid threonine at position 380 (written as Ala380Thr or A380T). The effect of this mutation is unknown, but it may impair the assembly of neurofilaments.
It is not known how NEFH mutations increase the risk of developing amyotrophic lateral sclerosis. Disrupted cross-linking or assembly of neurofilaments may lead to the accumulation of these filaments in motor neurons. Deposits of neurofilaments in deteriorating motor neurons appear to be an early feature of amyotrophic lateral sclerosis. It is unclear, however, whether these deposits play a role in causing this disorder or are a byproduct of dying motor neurons.
Where is the NEFH gene located?
Cytogenetic Location: 22q12.2
Molecular Location on chromosome 22: base pairs 28,206,218 to 28,217,278
The NEFH gene is located on the long (q) arm of chromosome 22 at position 12.2.
More precisely, the NEFH gene is located from base pair 28,206,218 to base pair 28,217,278 on chromosome 22.
See How do geneticists indicate the location of a gene? in the Handbook.
Where can I find additional information about NEFH?
You and your healthcare professional may find the following resources about NEFH helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed
- Recent literature
- OMIM
- Genetic disorder catalog
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What other names do people use for the NEFH gene or gene products?
- neurofilament triplet H protein
- NFH
- NFH_HUMAN
Where can I find general information about genes?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding NEFH?
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
healthcare professional.
See How can I find a genetics professional in my area? in the Handbook.