NEFM
protein-codingneurofilament medium chain, the group of Intermediate filaments Type IV
Gene summary
Neurofilaments are type IV intermediate filament heteropolymers composed of light, medium, and heavy chains. Neurofilaments comprise the axoskeleton and functionally maintain neuronal caliber. They may also play a role in intracellular transport to axons and dendrites. This gene encodes the medium neurofilament protein. This protein is commonly used as a biomarker of neuronal damage. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]
- NEF3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NEFM variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005382.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | 4 | |||
| missense | 126 | 2 | 1 | 129 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 128 | 2 | 3 | 133 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005373.2 | 3 | MANE Select | |
| Ensembl | ENSP00000221166.5 | 3 | MANE Select | |
| RefSeq | NP_001099011.1 | 2 | Standard | |
| Ensembl | ENSP00000412295.2 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)
- Amyotrophic lateral sclerosis (ALS)
- Association Between Physico-Chemical Features and Toxicity Associated Pathways
Biological Process
- neurofilament bundle assembly
- axon development
Molecular Function
- structural constituent of cytoskeleton
- protein binding
- microtubule binding
Cellular Component
- neurofilament
- axon
- intermediate filament cytoskeleton
- neurofibrillary tangle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000221166
- Coding exons
- 3
- Length
- 6083
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125748
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0678 | 463 | 459 | 1.01 | 0.0000228 | 5962 |
| Missense (PolyPhen) | 63 | 58.208 | 1.0823 | 854 | ||
| Synonymous | -0.894 | 209 | 193 | 1.08 | 0.0000105 | 1759 |
| Loss of Function | 3.61 | 9 | 30.5 | 0.295 | 0.00000144 | 456 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000064 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000056 | 0.000053 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Neurofilaments usually contain three intermediate filament proteins: L, M, and H which are involved in the maintenance of neuronal caliber.;
Recessive Scores
- pRec
- 0.351
Intolerance Scores
- LoFtool
- 0.0191
- RVIS EVS
- 0.25
- RVIS percentile EVS
- 69.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.831
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |