NTN1

Chr 17AD

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]

Primary Disease Associations & Inheritance

Mirror movements 4MIM #618264
AD
129
ClinVar variants
13
Pathogenic / LP
1.00
pLI score· haploinsufficient
2
Active trials
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.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 91 VUS of 129 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.60–0.74)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 1 / 21.4Missense obs/exp: 248 / 371.2Syn Z: 0.82

ClinVar Variant Classifications

129 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
2
11
0
13
Likely Pathogenic
0
0
0
0
0
VUS
1
83
7
0
91
Likely Benign
0
3
3
13
19
Benign
0
0
1
5
6
Total1882218129

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
NETRIN 1; NTN1
MIM #601614 · *

Mirror movements 4

MIM #618264

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — NTN1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Microbiota and Inflammatory Markers: A Review of Their Interplay, Clinical Implications, and Metabolic Disorders.
Peña-Durán E et al.·Int J Mol Sci
2025Review
The functional variant of NTN1 contributes to the risk of nonsyndromic cleft lip with or without cleft palate.
Li D et al.·Eur J Hum Genet
2020Functional
Defining the Genetic Landscape of Congenital Mirror Movements in 80 Affected Individuals.
Collins Hutchinson ML et al.·Mov Disord
2024
Comprehensive pan-cancer analysis reveals NTN1 as an immune infiltrate risk factor and its potential prognostic value in SKCM.
Luan F et al.·Sci Rep
2025
A heritable netrin-1 mutation increases atherogenic immune responses.
Schlegel M et al.·Atherosclerosis
2020
A Novel De Novo Missense Variant in Netrin-1 (NTN1) Associated With Chorioretinal Coloboma, Sensorineural Hearing Loss and Polydactyly.
Toms M et al.·Clin Genet
2025Case report
Human Macrophage Long Intergenic Noncoding RNA, SIMALR, Suppresses Inflammatory Macrophage Apoptosis via NTN1 (Netrin-1).
Cynn E et al.·Arterioscler Thromb Vasc Biol
2023
Locus and gene-based GWAS meta-analysis identifies new diabetic nephropathy genes.
Saeed M·Immunogenetics
2018Meta-analysis
Variants in CALD1, ESRP1, and RBFOX1 are associated with orofacial cleft risk.
Carlson JC et al.·PLoS Genet
2025Meta-analysis
Netrin-1 - DCC Signaling Systems and Age-Related Macular Degeneration.
SanGiovanni JP et al.·PLoS One
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Advanced Solid TumorsMetastatic Solid Tumors

NP137 Clinical and Biological Activities Assessment in Patients With Advanced/Metastatic Solid Tumors Treated by Standard Anti PD-1/PD-L1 Immunotherapies

ACTIVE NOT RECRUITING
NCT05605496Phase PHASE2Centre Leon BerardStarted 2023-01-06
NP137anti-PD-1/PD-L1
Pancreatic Cancer

Study of Perioperative NP137 and FOLFIRINOX in Resectable Pancreatic Cancer

NOT YET RECRUITING
NCT06203821Phase PHASE1Aram HezelStarted 2026-09-01
NP137

External Resources

Links to major genomics databases and tools