Seroatlas · Human Serome Atlas

NEFH

Neurofilament heavy polypeptide

Also known as: NF-H, NFH, NFH_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P12036
Gene: NEFH
Ensembl: ENSG00000100285
Chromosome: 22
Canonical length: 1020 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location: Nucleoplasm,Nuclear bodies,Primary cilium,Primary cilium transition zone,Centrosome,Basal body,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1020 residues, UniProt reviewed canonical sequence.

>P12036|NEFH
     1  MMSFGGADAL LGAPFAPLHG GGSLHYALAR KGGAGGTRSA AGSSSGFHSW TRTSVSSVSA
    61  SPSRFRGAGA ASSTDSLDTL SNGPEGCMVA VATSRSEKEQ LQALNDRFAG YIDKVRQLEA
   121  HNRSLEGEAA ALRQQQAGRS AMGELYEREV REMRGAVLRL GAARGQLRLE QEHLLEDIAH
   181  VRQRLDDEAR QREEAEAAAR ALARFAQEAE AARVDLQKKA QALQEECGYL RRHHQEEVGE
   241  LLGQIQGSGA AQAQMQAETR DALKCDVTSA LREIRAQLEG HAVQSTLQSE EWFRVRLDRL
   301  SEAAKVNTDA MRSAQEEITE YRRQLQARTT ELEALKSTKD SLERQRSELE DRHQADIASY
   361  QEAIQQLDAE LRNTKWEMAA QLREYQDLLN VKMALDIEIA AYRKLLEGEE CRIGFGPIPF
   421  SLPEGLPKIP SVSTHIKVKS EEKIKVVEKS EKETVIVEEQ TEETQVTEEV TEEEEKEAKE
   481  EEGKEEEGGE EEEAEGGEEE TKSPPAEEAA SPEKEAKSPV KEEAKSPAEA KSPEKEEAKS
   541  PAEVKSPEKA KSPAKEEAKS PPEAKSPEKE EAKSPAEVKS PEKAKSPAKE EAKSPAEAKS
   601  PEKAKSPVKE EAKSPAEAKS PVKEEAKSPA EVKSPEKAKS PTKEEAKSPE KAKSPEKEEA
   661  KSPEKAKSPV KAEAKSPEKA KSPVKAEAKS PEKAKSPVKE EAKSPEKAKS PVKEEAKSPE
   721  KAKSPVKEEA KTPEKAKSPV KEEAKSPEKA KSPEKAKTLD VKSPEAKTPA KEEARSPADK
   781  FPEKAKSPVK EEVKSPEKAK SPLKEDAKAP EKEIPKKEEV KSPVKEEEKP QEVKVKEPPK
   841  KAEEEKAPAT PKTEEKKDSK KEEAPKKEAP KPKVEEKKEP AVEKPKESKV EAKKEEAEDK
   901  KKVPTPEKEA PAKVEVKEDA KPKEKTEVAK KEPDDAKAKE PSKPAEKKEA APEKKDTKEE
   961  KAKKPEEKPK TEAKAKEDDK TLSKEPSKPK AEKAEKSSST DQKDSKPPEK ATEDKAAKGK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NEFH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.64
Highest tissue expression: 231 nTPM

Expression across tissuesHPA

Tissue

prostate: 231 nTPM
midbrain: 84 nTPM
cerebral cortex: 63 nTPM
hypothalamus: 51 nTPM
spinal cord: 44 nTPM
retina: 37 nTPM

Single-cell type

prostatic glandular cells: 1,739 nCPM
oocytes: 51 nCPM
differentiating spermatogonia: 43 nCPM
tuft cells: 35 nCPM
undifferentiated spermatogonia: 30 nCPM
other brain neurons: 25 nCPM

Immune cell

non-classical monocyte: 4.7 nTPM
intermediate monocyte: 2.7 nTPM
classical monocyte: 1 nTPM
MAIT T-cell: 0.8 nTPM
myeloid DC: 0.6 nTPM
total PBMC: 0.6 nTPM

Brain region

cerebral cortex: 1,218 nTPM
medulla oblongata: 1,093 nTPM
pons: 849 nTPM
thalamus: 410 nTPM
white matter: 364 nTPM
cerebellum: 352 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NEFH.

Disease | AllUniProt

Conditions NEFH is implicated in, by any mechanism.

Amyotrophic lateral sclerosis (ALS) MIM:105400
Charcot-Marie-Tooth disease, axonal, type 2CC (CMT2CC) MIM:616924

Disease | GeneticClinVar

9 pathogenic / likely-pathogenic of 1,118 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Charcot-Marie-Tooth disease axonal type 2CC
Hereditary neuropathy or pain disorder
Charcot-Marie-Tooth disease axonal type 2C
Inborn genetic diseases

Disease | ImmuneIEDB

Conditions an epitope on NEFH was assayed in.

sensory peripheral neuropathy B cell
allergic asthma T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 1.06
gnomAD pLI: 0
gnomAD missense Z: 0.52
DepMap mean gene effect: -0.05
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

Intermediate filament protein, conserved site
Intermediate filament, rod domain
Intermediate filament protein
Repeat of unknown function DUF1388
Repeat of unknown function (DUF1388)

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads NEFH as an antibody target. Whether an autoantibody or antibody against NEFH could matter depends on whether native NEFH is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NEFH is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label NEFH as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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