NTN1

Chr 17AD

netrin 1

Also known as: MRMV4, NET1, NTN1L

NCBI Gene: 9423ENSG00000065320UniProt: O95631OMIM: 601614

Netrin-1 is a secreted guidance protein that controls axon pathfinding during development by attracting or repelling growing axons depending on which receptors it binds. Mutations cause autosomal dominant mirror movements, a condition where voluntary movements on one side of the body are involuntarily mirrored on the opposite side due to abnormal crossing of motor pathways in the brainstem. The gene is highly constrained against loss-of-function variants (pLI 0.997, LOEUF 0.222), indicating that most protein-truncating variants are likely pathogenic.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.221 OMIM phenotype
Clinical Summary— NTN1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 91 VUS of 140 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — NTN1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 0.997
Z-score 4.08
OE 0.05 (0.02–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.27Z-score
OE missense 0.67 (0.60–0.74)
248 obs / 371.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.02–0.22)
0≤0.351.4
Missense OE0.67 (0.60–0.74)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 1 / 21.4Missense obs/exp: 248 / 371.2Syn Z: 0.82
DN
0.4189th %ile
GOF
0.4382th %ile
LOF
0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

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

140 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
VUS91
Likely Benign19
Benign6
13
Pathogenic
91
VUS
19
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
10
0
13
Likely Pathogenic
0
0
0
0
0
VUS
2
85
4
0
91
Likely Benign
0
3
3
13
19
Benign
0
0
1
5
6
Total2911818129

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

View in ClinVar →

Protein Context — Lollipop Plot

NTN1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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