NECTIN4

Chr 1

nectin 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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEctodermal dysplasia-syndactyly syndrome 1

Clinical highlights

Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
73
Pubs (1 yr)
P/LP submissions
P/LP missense
LOEUF
LOF
Mechanism· G2P
Some data sources returned errors (2)

gnomad: TimeoutError: The operation was aborted due to timeout

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

Constraint data not available from gnomAD.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NECTIN4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Muscle-Invasive Bladder CarcinomaMetastatic Urothelial Carcinoma

Modular Trial of sEphB4-HSA in EphrinB2-High Solid Tumors

RECRUITING
NCT06493552Phase PHASE2, PHASE3Vasgene Therapeutics, IncStarted 2025-03-15
SEphB4-HSAPembrolizumabGemcitabine
Advanced Malignant Solid NeoplasmMetastatic Malignant Solid Neoplasm

Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)

RECRUITING
NCT06311214Phase PHASE2National Cancer Institute (NCI)Started 2025-03-18
Biopsy ProcedureBiospecimen CollectionComputed Tomography
Urothelial CarcinomaBreast CancerLung Carcinoma

Clinical Application of PET Imaging Targeting Nectin-4 in Malignant Tumors

NOT YET RECRUITING
NCT06994078Phase NAUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyStarted 2025-07-01
68Ga-NOTA-Nectin-4 antibody fragment
Advanced Solid Tumors

A Study of AK146D1 for Injection in the Treatment of Advanced Solid Tumors

RECRUITING
NCT06929663Phase PHASE1AkesoStarted 2025-07-02
AK146D1 for injection
High-risk Muscle Invasive Urothelial Carcinoma

An Open-label Study to Investigate the Efficacy and Safety of Dato-DXd + Rilvegostomig vs SoC in Adult Participants With High-risk MIUC

RECRUITING
NCT07720284Phase PHASE3AstraZenecaStarted 2026-07-16
Dato-DXdRilvegostomigDurvalumab
Advanced or Metastatic Solid Tumors

Safety and Tolerability of IPH4502 in Patients With Advanced Solid Tumors

ACTIVE NOT RECRUITING
NCT06781983Phase PHASE1Innate PharmaStarted 2025-01-24
IPH4502
Non-Small Cell Lung Cancer

Zelenectide Pevedotin in NECTIN4 Amplified Advanced or Metastatic Non-small Cell Lung Cancer

ACTIVE NOT RECRUITING
NCT06933329Phase PHASE2BicycleTx LimitedStarted 2025-07-18
Zelenectide pevedotin
Advanced Urothelial CancerMetastatic Urothelial Carcinoma

Study of GB-4362 With Enfortumab Vedotin and Pembrolizumab for Advanced Urothelial Cancer

RECRUITING
NCT07484022Phase PHASE1Generate BiomedicinesStarted 2026-06
GB-4362enfortumab vedotin (EV)Pembrolizumab
MalignancyDigestive CancerDigestive System Neoplasm

Target-specific immunoPET Imaging of Digestive System Carcinoma

RECRUITING
NCT06715839Phase NARenJi HospitalStarted 2024-12-04
[68Ga]Ga-DOTA-H2D3[18F]F-RESCA-RB14[68Ga]Ga-NOTA-T4
Advanced Non Small Cell Lung Cancer (NSCLC)

A Phase II Study of AK146D1 in Combination With AK112 in Advanced Non-Small Cell Lung Cancer

RECRUITING
NCT07669779Phase PHASE2AkesoStarted 2026-07-10
AK146D1 for injectionAK112 InjectionPlatinum chemotherapy
Locally Advanced Bladder Urothelial CarcinomaLocally Advanced Renal Pelvis Urothelial CarcinomaLocally Advanced Ureter Urothelial Carcinoma

Testing Combination Erdafitinib and Enfortumab Vedotin in Metastatic Bladder Cancer After Treatment With Chemotherapy and Immunotherapy

ACTIVE NOT RECRUITING
NCT04963153Phase PHASE1National Cancer Institute (NCI)Started 2022-07-07
Biospecimen CollectionBone ScanComputed Tomography
Non Small Cell Lung CancerCervical CancerHead and Neck Squamous Cell Cancer

A 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 INVITATION
NCT07218003Phase PHASE1Rondo TherapeuticsStarted 2025-11-17
RNDO-564Pembrolizumab