NEFL
Chr 8ADARneurofilament light chain
Also known as: CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL, PPP1R110
The protein encodes the light chain of neurofilaments, which are intermediate filament heteropolymers that comprise the axoskeleton and maintain neuronal caliber. Mutations cause Charcot-Marie-Tooth disease types 1F, 2E, and dominant intermediate G through a dominant-negative mechanism, though autosomal recessive inheritance has also been reported. These are peripheral neuropathies characterized by progressive weakness and sensory loss in the hands and feet.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
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
500 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 | 15 | 4 | 66 | 0 | 85 |
Likely Pathogenic | 4 | 7 | 1 | 0 | 12 |
VUS | 3 | 214 | 23 | 3 | 243 |
Likely Benign | 0 | 6 | 24 | 77 | 107 |
Benign | 0 | 0 | 12 | 1 | 13 |
Conflicting | — | 24 | |||
| Total | 22 | 231 | 126 | 81 | 484 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NEFL · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Natural History Study to TRACK Brain and Spinal Cord Changes in Individuals with Friedreich Ataxia (TRACK-FA)
ACTIVE NOT RECRUITINGPhase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
ACTIVE NOT RECRUITINGHereditary Ataxia Research on Multi-Omics and Neuroclinical Insights in the Yangtze Delta
RECRUITINGAlzheimer's Disease Multinuclear Imaging Neuro-Enhanced Resolution (AD-MINER)
RECRUITINGA Study to Evaluate AB-1001 Striatal Administration in Adults With Early Manifest Huntington's Disease
ACTIVE NOT RECRUITINGBiomarker-based Trial of NPC-1 for Alzheimer's Pathology
RECRUITINGIndole-3-PROpionic Acid Clinical Trials - Multiple Sclerosis
RECRUITINGSafety, Tolerability and Exploratory Efficacy of EC5026 in Parkinson's Disease (STEP Study)
RECRUITINGAntibody-mediated NMDA Receptor Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Prolonged Recovery Stage
RECRUITINGStudy of Safety, Tolerability and Efficacy of PBGM01 in Pediatric Participants With GM1 Gangliosidosis
ACTIVE NOT RECRUITINGBiology-Driven Cognitive Profiling in Huntington's Disease
ACTIVE NOT RECRUITINGGAIN Symptoms: Post-traumatic Headache
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools