NEFM (Neurofilament Medium Chain) Gene
A key intermediate filament gene involved in neuronal cytoskeleton structure and axonal transport; associated with Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis.
Gene Information Card
| Symbol | NEFM |
|---|---|
| Full Name | Neurofilament Medium Chain |
| Gene Type | Protein coding |
| Chromosomal Location | 8p21.2 |
| NCBI Gene ID | 4741 ncbi.nlm.nih.gov/gene/4741 |
| Ensembl ID | ENSG00000104722 |
| UniProt ID | P07197 |
| OMIM ID | 162250 |
| HGNC ID | 7734 |
| Aliases | NF-M, NEF3, NFM |
Description
NEFM encodes the medium chain (160 kDa) of neurofilaments, a type IV intermediate filament that forms the neuronal cytoskeleton. Neurofilaments are essential for maintaining axonal caliber, structural integrity, and intracellular transport. NEFM assembles with neurofilament light (NEFL) and heavy (NEFH) chains to form heteropolymers. Mutations in NEFM are associated with Charcot-Marie-Tooth disease type 2E (CMT2E) and susceptibility to amyotrophic lateral sclerosis (ALS).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 2E (CMT2E) | Missense mutations disrupt neurofilament assembly, leading to axonal degeneration and peripheral neuropathy. | ClinVar, OMIM |
| Amyotrophic lateral sclerosis (ALS) | Variants in NEFM may contribute to motor neuron vulnerability by impairing axonal transport and increasing protein aggregation. | ClinVar, NCBI |
| Neurofilament accumulation disorders | Overexpression or aggregation of NEFM protein is observed in various neurodegenerative conditions, though direct causal evidence is limited. | NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Spinal cord | 10.8 | High |
| Peripheral nerve | 9.2 | High |
| Skeletal muscle | 0.3 | Low |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression; used in neuronal differentiation studies |
| U-87 MG (glioblastoma) | 2.1 | Moderate expression |
| HEK293 (embryonic kidney) | 0.0 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.698A>G (p.Glu233Gly) | Missense | Rare | Alters filament assembly; associated with CMT2E |
| c.1060C>T (p.Arg354Trp) | Missense | Rare | Disrupts neurofilament network; reported in ALS |
| c.1243G>A (p.Glu415Lys) | Missense | Rare | Potential loss of function; observed in CMT2E |
Mutation functional classification
Loss of Function (LOF)
Missense mutations impair neurofilament polymerization and axonal transport, leading to reduced structural integrity.
Gain of Function (GOF)
Not well established; some variants may promote protein aggregation.
Dominant Negative (DN)
Mutant NEFM can interfere with wild-type neurofilament assembly, causing dominant axonal degeneration in CMT2E.
View complete mutation data：
Gene Ontology (GO)
| • structural molecule activity (GO:0005198) | • intermediate filament (GO:0005882) |
| • cytoskeletal protein binding (GO:0008092) | • neuron projection (GO:0043005) |
| • cytoskeleton organization (GO:0007010) |
Pathways
• Intermediate filament polymerization (Reactome: R-HSA-6809371)
• Axonal transport (KEGG: hsa04728)
• Neurofilament assembly (GO:0033693)
Protein Summary
The neurofilament medium chain (NF-M) is a 160 kDa type IV intermediate filament protein expressed predominantly in neurons. It contains a central alpha-helical rod domain flanked by non-helical head and tail domains. NF-M co-assembles with NEFL and NEFH to form neurofilaments that provide mechanical support and regulate axonal diameter. Phosphorylation of the tail domain modulates filament spacing and transport. Mutations in NEFM cause Charcot-Marie-Tooth disease type 2E and are implicated in ALS.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NEFM Knockout HEK293 Cell Line | EDJ-KQ2580 | Human | 4741 | Details Get a Quote |
| NEFM Knockout HeLa Cell Line | EDJ-KQ53981 | Human | 4741 | Details Get a Quote |
| NEFM Knockout A-549 Cell Line | EDJ-KQ62471 | Human | 4741 | Details Get a Quote |
| NEFM Knockout HCT 116 Cell Line | EDJ-KQ70938 | Human | 4741 | Details Get a Quote |
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