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)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
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)