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NEFH neurofilament heavy chain [ Homo sapiens (human) ]

Gene ID: 4744, updated on 5-Sep-2025
Official Symbol
NEFHprovided by HGNC
Official Full Name
neurofilament heavy chainprovided by HGNC
Primary source
HGNC:HGNC:7737
See related
Ensembl:ENSG00000100285 MIM:162230; AllianceGenome:HGNC:7737
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
NFH; CMT2CC
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 heavy neurofilament protein. This protein is commonly used as a biomarker of neuronal damage and susceptibility to amyotrophic lateral sclerosis (ALS) has been associated with mutations in this gene. [provided by RefSeq, Oct 2008]
Expression
Biased expression in prostate (RPKM 140.1), brain (RPKM 16.4) and 2 other tissues See more
Orthologs
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See NEFH in Genome Data Viewer
Location:
22q12.2
Exon count:
4
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (29480218..29491390)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (29943567..29954761)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (29876207..29887379)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene ret finger protein like 1 Neighboring gene RFPL1 antisense RNA 1 Neighboring gene uncharacterized LOC107985541 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29856012-29856563 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29859341-29859868 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29859869-29860396 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29866133-29866633 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29874167-29874668 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29877229-29878083 Neighboring gene THO complex subunit 5 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29947869-29948568 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13592 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:29949966-29950663 Neighboring gene nipsnap homolog 1 Neighboring gene Sharpr-MPRA regulatory region 2653 Neighboring gene Sharpr-MPRA regulatory region 10387 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29976263-29976875 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13593

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. pNfH is a promising biomarker for ALS. Ganesalingam J, et al. Amyotroph Lateral Scler Frontotemporal Degener, 2013 Mar. PMID 23134506
  2. Cryptic amyloidogenic elements in mutant NEFH causing Charcot-Marie-Tooth 2 trigger aggresome formation and neuronal death. Jacquier A, et al. Acta Neuropathol Commun, 2017 Jul 14. PMID 28709447, Free PMC Article
  3. Phosphorylated neurofilament heavy chain: A biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis. Gendron TF, et al. Ann Neurol, 2017 Jul. PMID 28628244, Free PMC Article
  4. Phosphorylated neurofilament heavy chain levels in paired plasma and CSF of amyotrophic lateral sclerosis. Li S, et al. J Neurol Sci, 2016 Aug 15. PMID 27423602
  5. Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS. Oeckl P, et al. Amyotroph Lateral Scler Frontotemporal Degener, 2016 Jul-Aug. PMID 27415180

See all (100) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Neurodegeneration Markers in the Cerebrospinal Fluid of 100 Patients with Schizophrenia Spectrum Disorder.
    Title: Neurodegeneration Markers in the Cerebrospinal Fluid of 100 Patients with Schizophrenia Spectrum Disorder.
  2. Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset.
    Title: Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset.
  3. An NEFH founder mutation causes broad phenotypic spectrum in multiple Japanese families.
    Title: An NEFH founder mutation causes broad phenotypic spectrum in multiple Japanese families.
  4. Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype.
    Title: Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype.
  5. Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury.
    Title: Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury.
  6. Diagnostic and prognostic value of CSF neurofilaments in a cohort of patients with motor neuron disease: A cross-sectional study.
    Title: Diagnostic and prognostic value of CSF neurofilaments in a cohort of patients with motor neuron disease: A cross-sectional study.
  7. A novel missense pathogenic variant in NEFH causing rare Charcot-Marie-Tooth neuropathy type 2CC.
    Title: A novel missense pathogenic variant in NEFH causing rare Charcot-Marie-Tooth neuropathy type 2CC.
  8. Novel 199 base pair NEFH promoter drives expression in retinal ganglion cells.
    Title: Novel 199 base pair NEFH promoter drives expression in retinal ganglion cells.
  9. association of high preoperative serum level with postoperative cognitive dysfunction following hip arthroplasty suggests close association between anatomical central nervous system damage and postoperative cognitive dysfunction
    Title: Serum Phosphorylated Neurofilament Heavy Subunit-H, a Potential Predictive Biomarker for Postoperative Cognitive Dysfunction in Elderly Subjects Undergoing Hip Joint Arthroplasty.
  10. Serum pNF-H could be an objective delirium biomarker, superior to conventional tools in clinical settings.
    Title: Dysfunction of the blood-brain barrier in postoperative delirium patients, referring to the axonal damage biomarker phosphorylated neurofilament heavy subunit.
Submit: New GeneRIF Correction See all GeneRIFs (52)

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2025-07-08)

ClinGen Genome Curation Page
Haploinsufficency

No evidence available (Last evaluated 2025-07-08)

ClinGen Genome Curation PagePubMed

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables dynein complex binding TAS
Traceable Author Statement
more info
 PubMed 
enables kinesin binding TAS
Traceable Author Statement
more info
 PubMed 
enables microtubule binding TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-macromolecule adaptor activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables structural constituent of cytoskeleton IEA
Inferred from Electronic Annotation
more info
  
enables structural constituent of cytoskeleton IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables structural constituent of cytoskeleton ISS
Inferred from Sequence or Structural Similarity
more info
  
enables structural constituent of postsynaptic intermediate filament cytoskeleton IBA
Inferred from Biological aspect of Ancestor
more info
  
enables structural constituent of postsynaptic intermediate filament cytoskeleton IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in axon development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in axon development IEA
Inferred from Electronic Annotation
more info
  
involved_in axon development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in axonogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in axonogenesis TAS
Traceable Author Statement
more info
 PubMed 
involved_in cell projection assembly TAS
Traceable Author Statement
more info
 PubMed 
acts_upstream_of_or_within cellular response to leukemia inhibitory factor IEA
Inferred from Electronic Annotation
more info
  
involved_in intermediate filament bundle assembly IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within intermediate filament bundle assembly IEA
Inferred from Electronic Annotation
more info
  
involved_in intermediate filament bundle assembly IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within intermediate filament cytoskeleton organization IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within microtubule cytoskeleton organization IEA
Inferred from Electronic Annotation
more info
  
involved_in neurofilament bundle assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within neurofilament cytoskeleton organization IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within peripheral nervous system neuron axonogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in postsynaptic intermediate filament cytoskeleton organization IEA
Inferred from Electronic Annotation
more info
  
involved_in postsynaptic modulation of chemical synaptic transmission IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of organelle transport along microtubule IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
is_active_in Schaffer collateral - CA1 synapse IEA
Inferred from Electronic Annotation
more info
  
is_active_in axon IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in axon IEA
Inferred from Electronic Annotation
more info
  
located_in axon TAS
Traceable Author Statement
more info
 PubMed 
located_in cell projection IEA
Inferred from Electronic Annotation
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytoskeleton IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoskeleton IEA
Inferred from Electronic Annotation
more info
  
located_in intermediate filament IEA
Inferred from Electronic Annotation
more info
  
located_in neurofibrillary tangle IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in neurofilament IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in neurofilament IEA
Inferred from Electronic Annotation
more info
  
located_in neurofilament NAS
Non-traceable Author Statement
more info
 PubMed 
located_in postsynaptic density IEA
Inferred from Electronic Annotation
more info
  
is_active_in postsynaptic intermediate filament cytoskeleton IEA
Inferred from Electronic Annotation
more info
  
Preferred Names
neurofilament heavy polypeptide
Names
200 kDa neurofilament protein
NF-H
neurofilament triplet H protein
neurofilament, heavy polypeptide 200kDa
NP_066554.2

Length

  • 1020

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008404.1 RefSeqGene

    Range
    5027..16199
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_021076.4 → NP_066554.2  neurofilament heavy polypeptide

    See identical proteins and their annotated locations for NP_066554.2

    Status: REVIEWED

    Source sequence(s)
    AC000035, AF203032
    Consensus CDS
    CCDS13858.1
    UniProtKB/Swiss-Prot
    B4DYY4, P12036, Q96HF8, Q9UJS7, Q9UQ14
    Related
    ENSP00000311997.6, ENST00000310624.7
    Conserved Domains (2) summary
    PTZ00121
    Location:290 → 1014
    PTZ00121; MAEBL; Provisional
    pfam00038
    Location:96 → 412
    Filament; Intermediate filament protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    29480218..29491390
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011530200.3 → XP_011528502.1  neurofilament heavy polypeptide isoform X1

    Conserved Domains (2) summary
    pfam00038
    Location:96 → 412
    Filament; Intermediate filament protein
    pfam07142
    Location:536 → 562
    DUF1388; Repeat of unknown function (DUF1388)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    29943567..29954761
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P12036.5 GenPept UniProtKB/Swiss-Prot:P12036

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
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