NEFH Gene - Neurofilament Heavy Chain
Key structural component of neuronal intermediate filaments, implicated in neurodegenerative diseases and cancer.
Gene Information Card
| Symbol | NEFH |
|---|---|
| Full Name | Neurofilament Heavy Chain |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.2 |
| NCBI Gene ID | 4744 ncbi.nlm.nih.gov/gene/4744 |
| Ensembl ID | ENSG00000100285 |
| UniProt ID | P12036 |
| OMIM ID | 162230 |
| HGNC ID | 7737 |
| Aliases | NF-H, NEFH, CMT2CC, NFH |
Description
The NEFH gene encodes the neurofilament heavy polypeptide (NF-H), a major component of neuronal intermediate filaments. NF-H is essential for the maintenance of neuronal caliber, axonal transport, and structural integrity of neurons. Mutations in NEFH are associated with amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth disease type 2CC (CMT2CC).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic Lateral Sclerosis (ALS) | Dominant mutations in the KSP repeat domain cause aggregation and impaired axonal transport, leading to motor neuron degeneration. | ClinVar, OMIM |
| Charcot-Marie-Tooth Disease Type 2CC (CMT2CC) | Loss-of-function mutations disrupt neurofilament assembly, causing peripheral neuropathy. | ClinVar, OMIM |
| Frontotemporal Dementia (FTD) | Rare variants may contribute to TDP-43 pathology, though evidence is limited. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebral cortex | 12.5 | Medium |
| Spinal cord | 18.2 | High |
| Cerebellum | 15.0 | High |
| Peripheral nerve | 22.1 | High |
| Skeletal muscle | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.4 | Neuronal model |
| U-87 MG (glioblastoma) | 1.2 | Low expression |
| HEK 293 (embryonic kidney) | 0.1 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2158C>T (p.Arg720Cys) | Missense | Rare | Impaired phosphorylation and aggregation |
| c.3019G>A (p.Glu1007Lys) | Missense | Rare | Disrupted filament assembly |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in NEFH cause haploinsufficiency, leading to reduced neurofilament heavy chain levels and axonal degeneration in CMT2CC.
Gain of Function (GOF)
Missense mutations in the KSP repeat domain (e.g., p.Arg720Cys) promote toxic aggregation and impair axonal transport in ALS.
Dominant Negative (DN)
Some missense mutations disrupt neurofilament assembly by interfering with wild-type NF-H incorporation into filaments.
View complete mutation data：
Gene Ontology (GO)
| • intermediate filament (GO:0005882) | • structural molecule activity (GO:0005198) |
| • cytoskeletal protein binding (GO:0008092) | • neuron projection (GO:0043005) |
| • cytoskeleton organization (GO:0007010) |
Pathways
• Intermediate filament organization (Reactome: R-HSA-6809371)
• Neurofilament cytoskeleton (KEGG: hsa04540)
Protein Summary
Neurofilament heavy chain (NF-H) is a 200 kDa intermediate filament protein expressed predominantly in mature neurons. It contains a long C-terminal tail with multiple lysine-serine-proline (KSP) repeats that are heavily phosphorylated, regulating axonal caliber and stability. NF-H interacts with other neurofilament subunits (NF-L, NF-M) to form heteropolymers. Mutations in NEFH cause neurodegenerative diseases by disrupting filament assembly or promoting aggregation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NEFH Knockout HEK293 Cell Line | EDJ-KQ3049 | Human | 4744 | Details Get a Quote |
| NEFH Knockout HeLa Cell Line | EDJ-KQ24297 | Human | 4744 | Details Get a Quote |
| NEFH Knockout A-549 Cell Line | EDJ-KQ62472 | Human | 4744 | Details Get a Quote |
| NEFH Knockout HCT 116 Cell Line | EDJ-KQ70939 | Human | 4744 | Details Get a Quote |
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