NTNG2

Chr 9AR

netrin G2

Also known as: LHLL9381, Lmnt2, NEDBASH, NTNG1, NetrinG2, bA479K20.1

NCBI Gene: 84628ENSG00000196358UniProt: Q96CW9

Predicted to be involved in axonogenesis; regulation of cell projection organization; and regulation of neuron migration. Predicted to be located in plasma membrane. Predicted to be active in Schaffer collateral - CA1 synapse; glutamatergic synapse; and presynaptic active zone membrane. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotoniaMIM #618718
AR
141
ClinVar variants
43
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— NTNG2
⚡
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
43 Pathogenic / Likely Pathogenic· 70 VUS of 141 total submissions

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.
0.20LOEUF
pLI 0.999
Z-score 4.31
OE 0.04 (0.01–0.20)
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.
2.93Z-score
OE missense 0.55 (0.49–0.63)
191 obs / 344.2 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.0.04 (0.01–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.49–0.63)
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.0.88
0≤1.21.6
LoF obs/exp: 1 / 23.6Missense obs/exp: 191 / 344.2Syn Z: 1.14

ClinVar Variant Classifications

141 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic7
VUS70
Likely Benign16
Benign4
Conflicting1
36
Pathogenic
7
Likely Pathogenic
70
VUS
16
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
35
0
36
Likely Pathogenic
0
6
1
0
7
VUS
1
58
11
0
70
Likely Benign
0
2
2
12
16
Benign
0
1
1
2
4
Conflicting
—1
Total2675014134

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

View in ClinVar →

Protein Context — Lollipop Plot

NTNG2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NTNG2-related developmental delay, hypotonia, and autistic features

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
NETRIN G2; NTNG2
MIM #618689 · *

Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia

MIM #618718

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools