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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NFASC
neurofascin
Chromosome 1 Β· 1q32.1
NCBI Gene: 23114Ensembl: ENSG00000163531.17HGNC: HGNC:29866UniProt: A0A386QWI1
69PubMed Papers
21Diseases
0Drugs
13Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingplasma membranefocal adhesionbrain developmentneurodevelopmental disorder with central and peripheral motor dysfunctiongenetic disorderrisk-taking behaviourhair color
✦AI Summary

NFASC (neurofascin) encodes a cell adhesion protein that plays critical roles in nervous system development and function. The protein is essential for proper formation and maintenance of nodes of Ranvier and paranodal junctions in both central and peripheral nervous systems 1. NFASC exists in multiple isoforms, including neurofascin-155 (NF155) localized to paranodal regions and neurofascin-140/186 (NF140/186) found at nodes, where they interact with contactin-1 and contactin-associated protein 1 to maintain axo-glial integrity 2. Disease relevance includes autoimmune neuropathies where anti-neurofascin antibodies cause chr1 inflammatory demyelinating polyradiculoneuropathy (CIDP) and related conditions 13. Anti-pan-neurofascin antibodies induce severe, acute neuropathy with high morbidity through complement-mediated damage to nodes and paranodes 3. Genetic variants in NFASC have been identified as risk factors for progressive supranuclear palsy, suggesting broader neurological relevance 4. The protein is also implicated in intellectual disability and appears elevated in long COVID patients with cognitive impairment, indicating roles in nerve tissue repair 56. Clinical significance lies in antibody testing for accurate diagnosis of autoimmune neuropathies and guiding immunosuppressive treatment strategies.

Sources cited
1
NFASC antibodies are found in CIDP patients and localize to paranodal regions interacting with contactin-1 and CASPR1
PMID: 31753915
2
Neurofascin exists in multiple isoforms (NF155, NF140/186) with specific localizations at paranodes and nodes
PMID: 30582947
3
Anti-pan-neurofascin antibodies cause severe acute neuropathy through complement-mediated damage to nodes and paranodes
PMID: 36346134
4
NFASC genetic variants identified as risk factors for progressive supranuclear palsy
PMID: 40379966
5
NFASC variants proposed as novel candidates for intellectual disability
PMID: 28940097
6
NFASC elevated in long COVID patients with cognitive impairment, suggesting role in nerve tissue repair
PMID: 38589621
Disease Associationsβ“˜21
neurodevelopmental disorder with central and peripheral motor dysfunctionOpen Targets
0.78Strong
genetic disorderOpen Targets
0.42Moderate
risk-taking behaviourOpen Targets
0.38Weak
hair colorOpen Targets
0.36Weak
circadian rhythmOpen Targets
0.26Weak
neoplasmOpen Targets
0.24Weak
musculoskeletal system diseaseOpen Targets
0.24Weak
spondylolisthesisOpen Targets
0.24Weak
neurodegenerative diseaseOpen Targets
0.17Weak
neuromuscular diseaseOpen Targets
0.15Weak
amyotrophic lateral sclerosisOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
lung cancerOpen Targets
0.08Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
cystOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
posterior cortical atrophyOpen Targets
0.06Suggestive
hypertriglyceridemia 2Open Targets
0.06Suggestive
non-small cell lung carcinomaOpen Targets
0.06Suggestive
Neurodevelopmental disorder with central and peripheral motor dysfunctionUniProt
Pathogenic Variants13
NM_001160331.2(NFASC):c.2660G>A (p.Trp887Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 887
NM_001160331.2(NFASC):c.2616C>G (p.Tyr872Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 872
NM_001005388.3(NFASC):c.2579_2580del (p.Leu860fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2022β†’ Residue 860
NM_001005388.3(NFASC):c.2398C>T (p.Arg800Ter)Likely pathogenic
Neurodevelopmental disorder with central and peripheral motor dysfunction
β˜…β˜†β˜†β˜†2020β†’ Residue 800
NM_001005388.3(NFASC):c.3230T>C (p.Val1077Ala)Pathogenic
Neurodevelopmental disorder with central and peripheral motor dysfunction
β˜†β˜†β˜†β˜†2025β†’ Residue 1077
NM_001005388.3(NFASC):c.2458T>C (p.Ser820Pro)Pathogenic
Neurodevelopmental disorder with central and peripheral motor dysfunction
β˜†β˜†β˜†β˜†2025β†’ Residue 820
NM_001160331.2(NFASC):c.2816del (p.Pro939fs)Pathogenic
Neurodevelopmental disorder with central and peripheral motor dysfunction
β˜†β˜†β˜†β˜†2025β†’ Residue 939
NM_001005388.3(NFASC):c.2100C>A (p.Phe700Leu)Pathogenic
Neurodevelopmental disorder with central and peripheral motor dysfunction
β˜†β˜†β˜†β˜†2025β†’ Residue 700
NM_001160331.2(NFASC):c.2536C>T (p.Arg846Ter)Pathogenic
Neurodevelopmental disorder with central and peripheral motor dysfunction
β˜†β˜†β˜†β˜†2020β†’ Residue 846
NM_001160331.2(NFASC):c.2677C>T (p.Gln893Ter)Likely pathogenic
Neurodevelopmental disorder with central and peripheral motor dysfunction
β˜†β˜†β˜†β˜†2019β†’ Residue 893
NM_001005388.3(NFASC):c.3556G>T (p.Glu1186Ter)Likely pathogenic
Neurodevelopmental disorder with central and peripheral motor dysfunction
β˜†β˜†β˜†β˜†2019β†’ Residue 1186
NM_001005388.3(NFASC):c.3365T>A (p.Val1122Glu)Pathogenic
Neurodevelopmental disorder with central and peripheral motor dysfunction
β˜†β˜†β˜†β˜†2019β†’ Residue 1122
NM_001005388.3(NFASC):c.1076G>C (p.Arg359Pro)Pathogenic
Neurodevelopmental disorder with central and peripheral motor dysfunction
β˜†β˜†β˜†β˜†2019β†’ Residue 359
View on ClinVar β†—
Related Genes
PTPRBProtein interaction100%PTPRZ1Protein interaction100%PTPRZ2Protein interaction100%SCN8AProtein interaction100%SPTBN1Protein interaction100%CNTNAP1Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Ovary
51%
Heart
40%
Liver
15%
Lung
14%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
NFASCPTPRBPTPRZ1PTPRZ2SCN8ASPTBN1CNTNAP1
PROTEIN STRUCTURE
Preparing viewer…
PDB3P3Y Β· 2.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.36Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.28 [0.21–0.36]
RankingsWhere NFASC stands among ~20K protein-coding genes
  • #6,821of 20,598
    Most Researched69
  • #2,600of 5,498
    Most Pathogenic Variants13
  • #1,631of 17,882
    Most Constrained (LOEUF)0.36 Β· top 10%
Genes detectedNFASC
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Expanding the genetic heterogeneity of intellectual disability.
PMID: 28940097
Hum Genet Β· 2017
1.00
2
Integrative transcriptomic analysis of the amyotrophic lateral sclerosis spinal cord implicates glial activation and suggests new risk genes.
PMID: 36482247
Nat Neurosci Β· 2023
0.90
3
Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors.
PMID: 35685361
Comput Struct Biotechnol J Β· 2022
0.80
4
Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.
PMID: 38589621
Nat Immunol Β· 2024
0.70
5
A Spanish-Portuguese GWAS of progressive supranuclear palsy reveals a novel risk locus in NFASC.
PMID: 40379966
Eur J Hum Genet Β· 2025
0.60