NECTIN4
Chr 1ARnectin cell adhesion molecule 4
Also known as: EDSS1, LNIR, PRR4, PVRL4, nectin-4
This gene encodes a member of the nectin family. The encoded protein contains two immunoglobulin-like (Ig-like) C2-type domains and one Ig-like V-type domain. It is involved in cell adhesion through trans-homophilic and -heterophilic interactions. It is a single-pass type I membrane protein. The soluble form is produced by proteolytic cleavage at the cell surface by the metalloproteinase ADAM17/TACE. The secreted form is found in both breast tumor cell lines and breast tumor patients. Mutations in this gene are the cause of ectodermal dysplasia-syndactyly syndrome type 1, an autosomal recessive disorder. Alternatively spliced transcript variants have been found but the full-length nature of the variant has not been determined.[provided by RefSeq, Jan 2011]
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene — mechanism propensity
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
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
93 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 6 | 4 | 0 | 0 | 10 |
Likely Pathogenic | 1 | 1 | 0 | 0 | 2 |
VUS | 0 | 22 | 0 | 1 | 23 |
Likely Benign | 0 | 1 | 5 | 28 | 34 |
Benign | 0 | 4 | 2 | 6 | 12 |
Conflicting | — | 1 | |||
| Total | 7 | 32 | 7 | 35 | 82 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →12 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap NECTIN4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
NECTIN4 · 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
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
SC-101 in Subjects With Advanced NECTIN4-Amplified Cancers
NOT YET RECRUITINGEnfortumab Vedotin for the Treatment of Patients With Metastatic or Unresectable Squamous Cell Carcinoma of the Penis
RECRUITINGJS207 Combination Therapy in Triple-negative Breast Cancer
RECRUITINGA Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors
ACTIVE NOT RECRUITINGA Phase II Study of AK146D1 in Combination With AK112 in Advanced Non-Small Cell Lung Cancer
NOT YET RECRUITINGA Clinical Study of Multi-target Hi-TCR-T Cells in the Treatment of Advanced Hepatocellular Carcinoma
RECRUITINGDDR Genes Alteration and Response to Platinum-based Chemotherapy in Advanced Urothelial Cancer.
RECRUITINGA Biomarker Study to Predict Treatment Outcomes of Enfortumab Vedotin in Advanced Urothelial Carcinoma
ACTIVE NOT RECRUITING9MW2821 + Toripalimab vs 9MW2821 for 1st Line Locally Advanced or Metastatic Urothelial Carcinoma
RECRUITINGModular Trial of sEphB4-HSA in EphrinB2-High Solid Tumors
RECRUITINGCabozantinib in Combination With Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Cancer
RECRUITINGA Phase 1/1b of RNDO-564 Single Agent or in Combination With Pembrolizumab in Bladder Cancer and Other Solid Tumors Associated With Nectin-4
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools