NFASC

Chr 1

neurofascin

Also known as: NEDCPMD, NF, NRCAML

NCBI Gene: 23114 ENSG00000163531 UniProt: O94856

This protein is a cell adhesion molecule that organizes the axon initial segment and nodes of Ranvier by clustering voltage-gated sodium channels and linking the extracellular matrix to the intracellular cytoskeleton. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with central and peripheral motor dysfunction. The gene is highly constrained against loss-of-function variants, indicating that heterozygous loss alone is typically tolerated.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with central and peripheral motor dysfunction

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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