NEFL

Chr 8

neurofilament light chain

Also known as: CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL, PPP1R110

NCBI Gene: 4747 ENSG00000277586 UniProt: P07196

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCharcot-Marie-Tooth disease, demyelinating, type 1F

UniProtCharcot-Marie-Tooth disease, axonal, type 2E

UniProtCharcot-Marie-Tooth disease, dominant intermediate G

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — NEFL

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in NEFL?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 87

734 rare PASS variants

Rare truncating (LoF)

1 in 4,200

63 rare PASS variants

Rare synonymous (reference)

1 in 120

343 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NEFL. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓