NECTIN3

Chr 3

nectin cell adhesion molecule 3

Also known as: CD113, CDW113, NECTIN-3, PPR3, PRR3, PVRL3, PVRR3

NCBI Gene: 25945ENSG00000177707UniProt: Q9NQS3OMIM: 607147

The NECTIN3 protein functions as a cell adhesion molecule that promotes cell-cell adhesion at adherens junctions and synapses, and plays a critical role in ocular development, particularly ciliary body morphology. Mutations cause congenital ocular defects with autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.37
Clinical Summary— NECTIN3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 7 VUS of 54 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.37LOEUF
pLI 0.916
Z-score 3.66
OE 0.14 (0.06–0.37)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.77Z-score
OE missense 0.87 (0.78–0.97)
245 obs / 281.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.06–0.37)
0≤0.351.4
Missense OE0.87 (0.78–0.97)
0≤0.61.4
Synonymous OE1.18
0≤1.21.6
LoF obs/exp: 3 / 21.2Missense obs/exp: 245 / 281.4Syn Z: -1.43
DN
0.6648th %ile
GOF
0.6930th %ile
LOF
0.4134th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median
LOFLOEUF 0.37

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

54 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
VUS7
Likely Benign8
Benign16
Conflicting1
15
Pathogenic
7
VUS
8
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
0
0
0
VUS
0
5
2
0
7
Likely Benign
0
3
1
4
8
Benign
0
4
10
2
16
Conflicting
—1
Total01228647

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

View in ClinVar →

Protein Context — Lollipop Plot

NECTIN3 · 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 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Rac1 and Nectin3 are essential for planar cell polarity-directed axon guidance in the peripheral auditory system.
Clancy S et al.·Development
2025
Early-life stress of limited bedding/nesting material induced recognition memory loss and decreased hippocampal VGluT1 and nectin3 levels in aged male mice.
He ZC et al.·Pharmacol Biochem Behav
2025
Dorsal CA1 NECTIN3 Reduction Mediates Early-Life Stress-Induced Object Recognition Memory Deficits in Adolescent Female Mice.
Ma YN et al.·Neurosci Bull
2025
Prefrontal Nectin3 Reduction Mediates Adolescent Stress-Induced Deficits of Social Memory, Spatial Working Memory, and Dendritic Structure in Mice.
Wang HL et al.·Neurosci Bull
2020Open Access
Prominent role of the Ig-like V domain in trans-interactions of nectins. Nectin3 and nectin 4 bind to the predicted C-C'-C"-D beta-strands of the nectin1 V domain.
Fabre S et al.·J Biol Chem
2002
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