NTN3
Chr 16netrin 3
Also known as: NTN2L
The protein functions as a guidance cue that controls the navigation of commissural axons in the central nervous system and peripheral motor axons during development. Mutations in this gene cause autosomal recessive spinal muscular atrophy with congenital bone fractures, characterized by severe motor neuron degeneration and skeletal abnormalities present from birth. This gene shows minimal constraint against loss-of-function variants in the population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
180 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 | 0 | 0 | 26 | 0 | 26 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 123 | 17 | 0 | 140 |
Likely Benign | 0 | 6 | 0 | 0 | 6 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 129 | 47 | 0 | 176 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NTN3 · 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 open access results found
External Resources
Links to major genomics databases and tools