NFASC

Protein identityUniProt · HPA

UniProt accession

O94856

Gene

NFASC

Ensembl

ENSG00000163531

Chromosome

1

Canonical length

1347 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes an L1 family immunoglobulin cell adhesion molecule with multiple IGcam and fibronectin domains. The protein functions in neurite outgrowth, neurite fasciculation, and organization of the axon initial segment (AIS) and nodes of Ranvier on axons during early development. Both the AIS and nodes of Ranvier contain high densities of voltage-gated Na+ (Nav) channels which are clustered by interactions with cytoskeletal and scaffolding proteins including this protein, gliomedin, ankyrin 3 (ankyrin-G), and betaIV spectrin. This protein links the AIS extracellular matrix to the intracellular cytoskeleton. This gene undergoes extensive alternative splicing, and the full-length nature of some variants has not been determined.[provided by RefSeq, May 2009]

Canonical amino-acid sequenceUniProt

1347 residues, UniProt reviewed canonical sequence.

>O94856|NFASC
     1  MARQPPPPWV HAAFLLCLLS LGGAIEIPMD PSIQNELTQP PTITKQSAKD HIVDPRDNIL
    61  IECEAKGNPA PSFHWTRNSR FFNIAKDPRV SMRRRSGTLV IDFRSGGRPE EYEGEYQCFA
   121  RNKFGTALSN RIRLQVSKSP LWPKENLDPV VVQEGAPLTL QCNPPPGLPS PVIFWMSSSM
   181  EPITQDKRVS QGHNGDLYFS NVMLQDMQTD YSCNARFHFT HTIQQKNPFT LKVLTTRGVA
   241  ERTPSFMYPQ GTASSQMVLR GMDLLLECIA SGVPTPDIAW YKKGGDLPSD KAKFENFNKA
   301  LRITNVSEED SGEYFCLASN KMGSIRHTIS VRVKAAPYWL DEPKNLILAP GEDGRLVCRA
   361  NGNPKPTVQW MVNGEPLQSA PPNPNREVAG DTIIFRDTQI SSRAVYQCNT SNEHGYLLAN
   421  AFVSVLDVPP RMLSPRNQLI RVILYNRTRL DCPFFGSPIP TLRWFKNGQG SNLDGGNYHV
   481  YENGSLEIKM IRKEDQGIYT CVATNILGKA ENQVRLEVKD PTRIYRMPED QVARRGTTVQ
   541  LECRVKHDPS LKLTVSWLKD DEPLYIGNRM KKEDDSLTIF GVAERDQGSY TCVASTELDQ
   601  DLAKAYLTVL ADQATPTNRL AALPKGRPDR PRDLELTDLA ERSVRLTWIP GDANNSPITD
   661  YVVQFEEDQF QPGVWHDHSK YPGSVNSAVL RLSPYVNYQF RVIAINEVGS SHPSLPSERY
   721  RTSGAPPESN PGDVKGEGTR KNNMEITWTP MNATSAFGPN LRYIVKWRRR ETREAWNNVT
   781  VWGSRYVVGQ TPVYVPYEIR VQAENDFGKG PEPESVIGYS GEDYPRAAPT EVKVRVMNST
   841  AISLQWNRVY SDTVQGQLRE YRAYYWRESS LLKNLWVSQK RQQASFPGDR LRGVVSRLFP
   901  YSNYKLEMVV VNGRGDGPRS ETKEFTTPEG VPSAPRRFRV RQPNLETINL EWDHPEHPNG
   961  IMIGYTLKYV AFNGTKVGKQ IVENFSPNQT KFTVQRTDPV SRYRFTLSAR TQVGSGEAVT
  1021  EESPAPPNEA TPTAAPPTLP PTTVGATGAV SSTDATAIAA TTEATTVPII PTVAPTTIAT
  1081  TTTVATTTTT TAAATTTTES PPTTTSGTKI HESAPDEQSI WNVTVLPNSK WANITWKHNF
  1141  GPGTDFVVEY IDSNHTKKTV PVKAQAQPIQ LTDLYPGMTY TLRVYSRDNE GISSTVITFM
  1201  TSTAYTNNQA DIATQGWFIG LMCAIALLVL ILLIVCFIKR SRGGKYPVRE KKDVPLGPED
  1261  PKEEDGSFDY SDEDNKPLQG SQTSLDGTIK QQESDDSLVD YGEGGEGQFN EDGSFIGQYT
  1321  VKKDKEETEG NESSEATSPV NAIYSLA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NFASC 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

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.36

Highest tissue expression

32 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NFASC.

Disease | AllUniProt

Conditions NFASC is implicated in, by any mechanism.

• Neurodevelopmental disorder with central and peripheral motor dysfunction (NEDCPMD) MIM:618356

Disease | GeneticClinVar

13 pathogenic / likely-pathogenic of 346 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with central and peripheral motor dysfunction
• Inborn genetic diseases

Disease | AutoantibodyPubMed

Conditions in which antibodies against NFASC are reported. Each links to that disease's full target list.

• Polyradiculoneuropathy, Chronic Inflammatory Demyelinating 43
• Peripheral Nervous System Diseases 12
• Guillain-Barre Syndrome 7
• Multiple Sclerosis 6
• Autoimmune Diseases of the Nervous System 5
• Encephalomyelitis, Autoimmune, Experimental 4
• Polyneuropathies 3

Showing 7 of 8 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for NFASC from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.22

gnomAD pLI

1

gnomAD missense Z

2.59

DepMap mean gene effect

0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axon guidance
• brain development
• cell-cell adhesion
• myelination
• peripheral nervous system development

Molecular functions

• cell-cell adhesion mediator activity

Cellular components

• axon
• axon initial segment
• ficolin-1-rich granule membrane
• focal adhesion
• node of Ranvier
• paranodal junction
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Fibronectin type III
• Immunoglobulin-like domain
• Immunoglobulin I-set
• Immunoglobulin-like beta-sandwich domain
• Immunoglobulin-like fold
• Neurofascin/L1/NrCAM, C-terminal domain
• Fibronectin type III superfamily
• Immunoglobulin-like domain superfamily
• Fibronectin type III domain
• Immunoglobulin domain
• Immunoglobulin I-set domain
• Bravo-like intracellular region
• Immunoglobulin domain
• Neurofascin, immunoglobulin-like domain

KeywordsUniProt

• Cell adhesion
• Cell junction
• Cell membrane
• Disulfide bond
• Glycoprotein
• Immunoglobulin domain
• Membrane
• Phosphoprotein
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of NFASC in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MYOC
• SCN3B
• SDCBP
• SCN1B