NECTIN3

Chr 3

nectin cell adhesion molecule 3

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

NCBI Gene: 25945ENSG00000177707UniProt: Q9NQS3OMIM: 607147

This gene encodes a member of the nectin family of proteins, which function as adhesion molecules at adherens junctions. This family member interacts with other nectin-like proteins and with afadin, a filamentous actin-binding protein involved in the regulation of directional motility, cell proliferation and survival. This gene plays a role in ocular development involving the ciliary body. Mutations in this gene are believed to result in congenital ocular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

OMIMResearchGenerating clinical summary…
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.
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ClinVar Variants
5 VUS of 37 total submissions
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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 OE?0.14 (0.06–0.37)
0≤0.351.4
Missense OE?0.87 (0.78–0.97)
0≤0.61.4
Synonymous OE?1.18
0≤1.21.6
LoF obs/exp: 3 / 21.2Missense obs/exp: 245 / 281.4Syn Z: -1.43

This gene — mechanism propensity

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

37 submitted variants in ClinVar

ClinVar

Classification Summary

VUS5
Likely Benign8
Benign16
Conflicting1
5
VUS
8
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
5
0
0
5
Likely Benign
0
3
1
4
8
Benign
0
4
10
2
16
Conflicting
—1
Total01211630

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap NECTIN3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

NECTIN3 · 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