NTN1

Chr 17

netrin 1

Also known as: MRMV4, NET1, NTN1L

NCBI Gene: 9423ENSG00000065320UniProt: O95631

Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon guidance and cell migration during development. Mutations and loss of expression of netrin suggest that variation in netrin may be involved in cancer development. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…
LOFmechanismLOEUF 0.22
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
3 unique Pathogenic / Likely Pathogenic· 88 VUS of 125 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 →
📖
GeneReview available — NTN1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.05 (0.02–0.22)
0≤0.351.4
Missense OE?0.67 (0.60–0.74)
0≤0.61.4
Synonymous OE?0.92
0≤1.21.6
LoF obs/exp: 1 / 21.4Missense obs/exp: 248 / 371.2Syn Z: 0.82

This gene — mechanism propensity

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

125 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
VUS88
Likely Benign17
Benign6
3
Pathogenic
88
VUS
17
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
0
0
3
Likely Pathogenic
0
0
0
0
0
VUS
2
85
1
0
88
Likely Benign
0
3
1
13
17
Benign
0
0
1
5
6
Total291318114

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap NTN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

NTN1 · 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