NEFL
  • 0
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
NEFL (HGNC:7739) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
neurofilament light chain
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
NFL, CMT1F, CMT2E, NF68, PPP1R110
%HI
0(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
0.99(Read more about gnomAD LOEUF score)
Cytoband
8p21.2
Genomic Coordinates
GRCh37/hg19: chr8:24808468-24814126 NCBI Ensembl UCSC
GRCh38/hg38: chr8:24950955-24956612 NCBI Ensembl UCSC
MANE Select Transcript
NM_006158.5 ENST00000610854.2 (Read more about MANE Select)
Function
Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal intermediate filament proteins PRPH and INA to form neuronal filamentous networks (By similarity). {ECO:0000250|UniProtKB:P08551}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-31091
ClinGen Curation ID:
CCID:007543
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency (0)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
09/17/2018

Haploinsufficiency (HI) Score Details

HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency (Disclaimer)
HI Evidence:
  • PUBMED: 20039262
    A homozygous E210X variant was identified in four affected siblings with severe, progressive, childhood neuropathy. Parents are consanguineous and unaffected heterozygous carriers. Functional studies support loss of function.
  • PUBMED: 19158810
    Abe et al. 2009: Charcot-Marie-Tooth (CMT) patients were screened for mutations via multi-gene panel testing. Four heterozygous missense and one homozygous p.E140* variant were detected in NEFL among 223 CMT patients. The parents of this patient were unaffected carriers and consanguineous.
HI Evidence Comments:
Heterozygous missense variants in NEFL typically cause Charcot-Marie-Tooth types 2E and 1F. Most pathogenic variants are transcribed and produce a protein that is defective in neurofilament assembly and transport. There are a few reports of nonsense variants in NEFL associated with disease. In addition to the family described in PMID 19158810, a homozygous p.E210* variant was associated with severe, progressive neuropathy. This was attributed to biallelic NEFL loss of function (PMID:20039262). In another family, a heterozygous p.R421* variant showed evidence of producing a stable transcript. The authors hypothesized that the translated mutated protein interfered with normal functioning of the wild-type protein, causing disease in the family (PMID: 25264603). There is no evidence to suggest that haploinsufficiency of NEFL would carry an abnormal phenotype.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No evidence of triplosensitivity for the NEFL gene.

Genomic View

Select assembly: (NC_000008.10) (NC_000008.11)