NECTIN3

Chr 3

nectin cell adhesion molecule 3

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

NCBI Gene: 25945 ENSG00000177707 UniProt: Q9NQS3 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.37

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in NECTIN3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

938 rare PASS variants

Rare truncating (LoF)

1 in 930

99 rare PASS variants

Rare synonymous (reference)

1 in 150

404 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NECTIN3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 67	1 in 1,700
South Asian	~43k	1 in 47	1 in 390
Remaining (unassigned)	~30k	1 in 48	1 in 690
European (Finnish)	~27k	1 in 120	1 in 3,400
Admixed American	~22k	1 in 57	1 in 890
African / African American	~21k	1 in 51	1 in 1,700
East Asian	~20k	1 in 81	1 in 470
Ashkenazi Jewish	~13k	1 in 150	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 68	1 in 560

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓