NAV3

Chr 12AR

neuron navigator 3

Also known as: NEDSFB, POMFIL1, STEERIN3, unc53H3

NCBI Gene: 89795ENSG00000067798UniProt: Q8IVL0

This gene belongs to the neuron navigator family and is expressed predominantly in the nervous system. The encoded protein contains coiled-coil domains and a conserved AAA domain characteristic for ATPases associated with a variety of cellular activities. This gene is similar to unc-53, a Caenorhabditis elegans gene involved in axon guidance. Multiple alternatively spliced transcript variants for this gene have been described but only one has had its full-length nature determined. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with poor or absent speech, dysmorphic facies, and behavioral abnormalitiesMIM #621182
AR
366
ClinVar variants
19
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— NAV3
⚡
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
19 Pathogenic / Likely Pathogenic· 294 VUS of 366 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.
0.18LOEUF
pLI 1.000
Z-score 8.42
OE 0.11 (0.07–0.18)
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.
1.33Z-score
OE missense 0.89 (0.85–0.94)
1127 obs / 1260.1 exp
Tolerant

Mild missense constraint

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.0.11 (0.07–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.85–0.94)
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.1.09
0≤1.21.6
LoF obs/exp: 12 / 105.2Missense obs/exp: 1127 / 1260.1Syn Z: -1.57

ClinVar Variant Classifications

366 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic2
VUS294
Likely Benign8
Benign8
17
Pathogenic
2
Likely Pathogenic
294
VUS
8
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
16
0
17
Likely Pathogenic
0
0
2
0
2
VUS
2
284
8
0
294
Likely Benign
0
4
1
3
8
Benign
0
3
0
5
8
Total3291278329

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

View in ClinVar →

Protein Context — Lollipop Plot

NAV3 · 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
NEURON NAVIGATOR 3; NAV3
MIM #611629 · *

Neurodevelopmental disorder with poor or absent speech, dysmorphic facies, and behavioral abnormalities

MIM #621182

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly.
Ghaffar A et al.·Commun Biol
2024
Microtubule-associated NAV3 regulates invasive phenotypes in glioblastoma cells.
Škarková A et al.·Brain Pathol
2025
Novel association of NAV3 with dilated cardiomyopathy and its role in cardiac fibrosis.
Wang M et al.·Am J Physiol Heart Circ Physiol
2026
Further evidence of biallelic NAV3 variants associated with recessive neurodevelopmental disorder with dysmorphism, developmental delay, intellectual disability, and behavioral abnormalities.
Kakar N et al.·Hum Genet
2025
IMOP-Cancer: identifying mutation order pairs impacting cancer phenotypes.
Zhang Y et al.·Brief Bioinform
2025
NAV3 Is a Novel Prognostic Biomarker Affecting the Immune Status of the Tumor Microenvironment in Colorectal Cancer.
Li M et al.·J Immunol Res
2022
Primary cutaneous T-cell lymphomas show a deletion or translocation affecting NAV3, the human UNC-53 homologue.
Karenko L et al.·Cancer Res
2005
Development of a prognostic model based on the ceRNA network in Triple-Negative Breast cancer.
Zhu Y et al.·PeerJ
2025Functional
Neuron navigator 3 alterations in nervous system tumors associate with tumor malignancy grade and prognosis.
Carlsson E et al.·Genes Chromosomes Cancer
2013
Mutated neuron navigator 3 as a candidate gene for a rare neurodevelopmental disorder.
Umair M et al.·Mol Genet Genomic Med
2024Case report
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