NFASC
Chr 1ARneurofascin
Also known as: NEDCPMD, NF, NRCAML
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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
371 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 3 | 5 | 15 | 0 | 23 |
Likely Pathogenic | 5 | 0 | 1 | 0 | 6 |
VUS | 4 | 199 | 10 | 0 | 213 |
Likely Benign | 0 | 29 | 11 | 29 | 69 |
Benign | 0 | 3 | 2 | 16 | 21 |
Conflicting | — | 8 | |||
| Total | 12 | 236 | 39 | 45 | 340 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NFASC · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools