NEFL
Chr 8ADARneurofilament light chain
Also known as: CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL, PPP1R110
Neurofilaments are type IV intermediate filament heteropolymers composed of light, medium, and heavy chains. Neurofilaments comprise the axoskeleton and they functionally maintain the neuronal caliber. They may also play a role in intracellular transport to axons and dendrites. This gene encodes the light chain neurofilament protein. Mutations in this gene cause Charcot-Marie-Tooth disease types 1F (CMT1F) and 2E (CMT2E), disorders of the peripheral nervous system that are characterized by distinct neuropathies. A pseudogene has been identified on chromosome Y. [provided by RefSeq, Oct 2008]
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
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Population Genetics & Constraint
Constraint data not available from gnomAD.
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports gain-of-function. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
497 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 6 | 0 | 46 | 0 | 52 |
Likely Pathogenic | 1 | 4 | 4 | 0 | 9 |
VUS | 4 | 254 | 30 | 4 | 292 |
Likely Benign | 0 | 4 | 27 | 89 | 120 |
Benign | 0 | 0 | 11 | 1 | 12 |
Conflicting | — | 12 | |||
| Total | 11 | 262 | 118 | 94 | 497 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →NEFL · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
An IIT Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of a Single Intrathecal Injection of SNUG01 in Patients with Amyotrophic Lateral Sclerosis
NOT YET RECRUITINGObservational Study of Neurofilament Light Chain (NfL) as a Biomarker in Asymptomatic Carriers of the Transthyretin (TTR) Variants and Patients With Hereditary Transthyretin-mediated (hATTR) Amyloidosis With Polyneuropathy
RECRUITINGChild to Adult Neurodevelopment in Gene Expanded Huntington's Disease
RECRUITINGA Study to Investigate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease
NOT YET RECRUITINGPhase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
ACTIVE NOT RECRUITINGAlzheimer's Disease Multinuclear Imaging Neuro-Enhanced Resolution (AD-MINER)
RECRUITINGDisease Biosignatures in ALS/FTD Spectrum: New Impactful Biological Perspectives Beyond Clinical Approaches
NOT YET RECRUITINGThis Study Evaluates the Safety, Target Engagement, and Preliminary Efficacy of Galunisertib (TGF-βR1/ALK5 Inhibitor)Combined With Nerandomilast (PDE4 Inhibitor) in GREM2-positive ALS, a Biomarker-defined Subgroup Hypothesized to Reflect Heightened TGF-β/SMAD-driven Astrocytic and Fibrotic Signaling
NOT YET RECRUITINGA Study to Learn About the Safety and Effects of Salanersen (BIIB115) When Given to Babies With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Onasemnogene Abeparvovec
NOT YET RECRUITINGA Natural History Study to TRACK Brain and Spinal Cord Changes in Individuals with Friedreich Ataxia (TRACK-FA)
ACTIVE NOT RECRUITINGA Study of BIIB067 (Tofersen) Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation
ACTIVE NOT RECRUITINGSafety and Efficacy of BAFF-R CART for Refractory Neuroimmune Diseases
RECRUITINGExternal Resources
Links to major genomics databases and tools