NTN3

Chr 16

netrin 3

Also known as: NTN2L

NCBI Gene: 4917ENSG00000162068OMIM: 602349

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in Golgi apparatus and extracellular region. [provided by Alliance of Genome Resources, Jul 2025]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.21
Clinical Summary— NTN3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
123 VUS of 133 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.21LOEUF
pLI 0.000
Z-score 0.94
OE 0.75 (0.48–1.21)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.28Z-score
OE missense 0.95 (0.87–1.05)
293 obs / 307.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.75 (0.48–1.21)
0≤0.351.4
Missense OE?0.95 (0.87–1.05)
0≤0.61.4
Synonymous OE?0.92
0≤1.21.6
LoF obs/exp: 12 / 16.1Missense obs/exp: 293 / 307.0Syn Z: 0.68

This gene — mechanism propensity

DN
0.6162th %ile
GOF
0.6736th %ile
LOF
0.3550th %ile

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.

GOFprediction above median
DNprediction above median

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

133 submitted variants in ClinVar

ClinVar

Classification Summary

VUS123
Likely Benign6
123
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
123
0
0
123
Likely Benign
0
6
0
0
6
Benign
0
0
0
0
0
Total012900129

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

30 pathogenic / likely-pathogenic (of 47) ClinVar copy-number / structural variants overlap NTN3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

NTN3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients