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 metallo... See more...

Aliases for NECTIN4 Gene

Aliases for NECTIN4 Gene

  • Nectin Cell Adhesion Molecule 4 2 3 4 5
  • Nectin-4 2 3 4
  • LNIR 2 3 4
  • PRR4 2 3 4
  • Poliovirus Receptor-Related Protein 4 3 4
  • Poliovirus Receptor-Related 4 2 3
  • Ig Superfamily Receptor LNIR 3 4
  • PVRL4 3 4
  • Nectin 4 3
  • NECTIN4 5
  • EDSS1 3

External Ids for NECTIN4 Gene

Previous HGNC Symbols for NECTIN4 Gene

  • PVRL4

Summaries for NECTIN4 Gene

Entrez Gene Summary for NECTIN4 Gene

  • 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]

CIViC Summary for NECTIN4 Gene

GeneCards Summary for NECTIN4 Gene

NECTIN4 (Nectin Cell Adhesion Molecule 4) is a Protein Coding gene. Diseases associated with NECTIN4 include Ectodermal Dysplasia-Syndactyly Syndrome 1 and Ectodermal Dysplasia. Among its related pathways are Adherens junction and Cell junction organization. An important paralog of this gene is NECTIN3.

UniProtKB/Swiss-Prot Summary for NECTIN4 Gene

  • Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvirus entry into cells.
  • (Microbial infection) Acts as a receptor for measles virus.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NECTIN4 Gene

Genomics for NECTIN4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NECTIN4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NECTIN4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NECTIN4

Genomic Locations for NECTIN4 Gene

Latest Assembly
chr1:161,070,998-161,089,566
(GRCh38/hg38)
Size:
18,569 bases
Orientation:
Minus strand

Previous Assembly
chr1:161,040,788-161,059,348
(GRCh37/hg19 by Entrez Gene)
Size:
18,561 bases
Orientation:
Minus strand

chr1:161,040,785-161,059,389
(GRCh37/hg19 by Ensembl)
Size:
18,605 bases
Orientation:
Minus strand

Genomic View for NECTIN4 Gene

Genes around NECTIN4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NECTIN4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NECTIN4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NECTIN4 Gene

Proteins for NECTIN4 Gene

  • Protein details for NECTIN4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96NY8-NECT4_HUMAN
    Recommended name:
    Nectin-4
    Protein Accession:
    Q96NY8
    Secondary Accessions:
    • B4DQW3
    • Q96K15

    Protein attributes for NECTIN4 Gene

    Size:
    510 amino acids
    Molecular mass:
    55454 Da
    Quaternary structure:
    • Self-associates. Interacts via its Ig-like V-type domain with NECTIN1 Ig-like V-type domain. Interacts via its C-terminus with AFDN.
    • (Microbial infection) Interacts with measles virus Hemagglutinin protein (PubMed:22048310, PubMed:23202587).

    Three dimensional structures from OCA and Proteopedia for NECTIN4 Gene

    Alternative splice isoforms for NECTIN4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NECTIN4 Gene

Post-translational modifications for NECTIN4 Gene

  • The soluble form is produced by proteolytic cleavage at the cell surface (shedding), probably by ADAM17/TACE.
  • Glycosylation at Asn281
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • NECT4_HUMAN (1538)

Other Protein References for NECTIN4 Gene

No data available for DME Specific Peptides for NECTIN4 Gene

Domains & Families for NECTIN4 Gene

Gene Families for NECTIN4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for NECTIN4 Gene

InterPro:
Blocks:
  • Immunoglobulin C-2 type
  • Immunoglobulin V-set

Suggested Antigen Peptide Sequences for NECTIN4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ61684, highly similar to Homo sapiens poliovirus receptor-related 4 (PVRL4), mRNA (B4DQW3_HUMAN)
  • Nectin-4 (PVRL4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96NY8

UniProtKB/Swiss-Prot:

NECT4_HUMAN :
  • Belongs to the nectin family.
Family:
  • Belongs to the nectin family.
genes like me logo Genes that share domains with NECTIN4: view

Function for NECTIN4 Gene

Molecular function for NECTIN4 Gene

UniProtKB/Swiss-Prot Function:
Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvirus entry into cells.
UniProtKB/Swiss-Prot Function:
(Microbial infection) Acts as a receptor for measles virus.

Phenotypes From GWAS Catalog for NECTIN4 Gene

Gene Ontology (GO) - Molecular Function for NECTIN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001618 virus receptor activity IEA --
GO:0005515 protein binding IPI 21982860
GO:0042802 identical protein binding IPI 22902367
genes like me logo Genes that share ontologies with NECTIN4: view
genes like me logo Genes that share phenotypes with NECTIN4: view

Human Phenotype Ontology for NECTIN4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NECTIN4

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for NECTIN4 Gene

Localization for NECTIN4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NECTIN4 Gene

Cell membrane. Single-pass type I membrane protein. Cell junction, adherens junction. Note=Colocalizes with AFDN at cadherin-based adherens junctions (PubMed:11544254).
[Processed poliovirus receptor-related protein 4]: Secreted. Note=The secreted form is found in breast tumor patients (PubMed:15784625).

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NECTIN4 gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytoskeleton 2
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NECTIN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005886 plasma membrane TAS --
GO:0005912 adherens junction IDA 25468996
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with NECTIN4: view

Pathways & Interactions for NECTIN4 Gene

PathCards logo

SuperPathways for NECTIN4 Gene

genes like me logo Genes that share pathways with NECTIN4: view

Pathways by source for NECTIN4 Gene

2 Qiagen pathways for NECTIN4 Gene
  • Epithelial Adherens Junctions
  • Sertoli-Sertoli Cell Junction Dynamics
1 Cell Signaling Technology pathway for NECTIN4 Gene

Gene Ontology (GO) - Biological Process for NECTIN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007155 cell adhesion IEA --
GO:0007156 homophilic cell adhesion via plasma membrane adhesion molecules IBA 21873635
GO:0007157 heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules IBA 21873635
GO:0016032 viral process IEA --
GO:0034332 adherens junction organization TAS --
genes like me logo Genes that share ontologies with NECTIN4: view

No data available for SIGNOR curated interactions for NECTIN4 Gene

Drugs & Compounds for NECTIN4 Gene

(3) Drugs for NECTIN4 Gene - From: DrugBank, PharmGKB, and DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
enfortumab vedotin Approved, Investigational Pharma Target, binder 0
Methadone Approved Pharma 418
ASG-22ME Pharma antibody 0
genes like me logo Genes that share compounds with NECTIN4: view

Transcripts for NECTIN4 Gene

mRNA/cDNA for NECTIN4 Gene

1 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NECTIN4

Alternative Splicing Database (ASD) splice patterns (SP) for NECTIN4 Gene

No ASD Table

Relevant External Links for NECTIN4 Gene

GeneLoc Exon Structure for
NECTIN4

Expression for NECTIN4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NECTIN4

mRNA Expression by UniProt/SwissProt for NECTIN4 Gene:

Q96NY8-NECT4_HUMAN
Tissue specificity: Predominantly expressed in placenta. Not detected in normal breast epithelium but expressed in breast carcinoma.

Evidence on tissue expression from TISSUES for NECTIN4 Gene

  • Pancreas(4.2)
  • Skin(2.6)
  • Lung(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NECTIN4 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • integumentary
  • skeleton
Regions:
Head and neck:
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • scalp
  • skull
  • tooth
Limb:
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • nail
  • toe
  • upper limb
General:
  • hair
  • skin
  • sweat gland
genes like me logo Genes that share expression patterns with NECTIN4: view

Primer products for research

No data available for mRNA expression in normal human tissues , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for NECTIN4 Gene

Orthologs for NECTIN4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NECTIN4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PVRL4 29 30
  • 99.67 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia PVRL4 29 30
  • 90.04 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PVRL4 29 30
  • 89.48 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Pvrl4 29
  • 88.39 (n)
Mouse
(Mus musculus)
Mammalia Pvrl4 29 30
  • 87.73 (n)
OneToOne
Nectin4 16
Oppossum
(Monodelphis domestica)
Mammalia PVRL4 30
  • 80 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia PVRL4 30
  • 62 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.13547 29
Zebrafish
(Danio rerio)
Actinopterygii LOC560512 29
  • 48.81 (n)
pvrl4 30
  • 26 (a)
OneToMany
PVRL4 (2 of 3) 30
  • 23 (a)
OneToMany
PVRL4 (3 of 3) 30
  • 14 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 16 (a)
OneToMany
Species where no ortholog for NECTIN4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for NECTIN4 Gene

ENSEMBL:
Gene Tree for NECTIN4 (if available)
TreeFam:
Gene Tree for NECTIN4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NECTIN4: view image
Alliance of Genome Resources:
Additional Orthologs for NECTIN4

Paralogs for NECTIN4 Gene

genes like me logo Genes that share paralogs with NECTIN4: view

Variants for NECTIN4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NECTIN4 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
1013259 Uncertain Significance: not provided 161,072,729(-) T/C
NM_030916.3(NECTIN4):c.1465A>G (p.Asn489Asp)
MISSENSE
1029983 Uncertain Significance: Ectodermal dysplasia-syndactyly syndrome 1 161,072,716(-) C/G
NM_030916.3(NECTIN4):c.1478G>C (p.Arg493Pro)
MISSENSE
1032239 Pathogenic: Ectodermal dysplasia-syndactyly syndrome 1 161,073,719(-) C/T
NM_030916.3(NECTIN4):c.1233+1G>A
SPLICE_DONOR
1032240 Uncertain Significance: Ectodermal dysplasia-syndactyly syndrome 1 161,072,807(-) G/C
NM_030916.3(NECTIN4):c.1387C>G (p.Pro463Ala)
MISSENSE
996828 Pathogenic: Ectodermal dysplasia-syndactyly syndrome 1 161,074,731(-) G/A
NM_030916.3(NECTIN4):c.880C>T (p.Arg294Ter)
NONSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for NECTIN4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for NECTIN4 Gene

Variant ID Type Subtype PubMed ID
esv3351730 CNV duplication 20981092
esv988172 CNV deletion 20482838
nsv1161729 CNV duplication 26073780
nsv3221 CNV deletion 18451855

Variation tolerance for NECTIN4 Gene

Residual Variation Intolerance Score: 51.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.40; 63.69% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NECTIN4 Gene

Human Gene Mutation Database (HGMD)
NECTIN4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NECTIN4
Leiden Open Variation Database (LOVD)
NECTIN4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NECTIN4 Gene

Disorders for NECTIN4 Gene

MalaCards: The human disease database

(8) MalaCards diseases for NECTIN4 Gene - From: CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

NECT4_HUMAN
  • Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) [MIM:613573]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDSS1 is characterized by the association of hair and teeth abnormalities with cutaneous syndactyly of the hands and/or feet. Hair morphologic abnormalities include twists at irregular intervals (pilli torti) and swelling along the shafts, particularly associated with areas of breakage. Dental findings consist of abnormally widely spaced teeth, with peg-shaped and conical crowns. Patients have normal sweating. {ECO:0000269 PubMed:20691405}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for NECTIN4

genes like me logo Genes that share disorders with NECTIN4: view

No data available for Genatlas for NECTIN4 Gene

Publications for NECTIN4 Gene

  1. Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome. (PMID: 20691405) Brancati F … Dallapiccola B (American journal of human genetics 2010) 3 4 72
  2. Nectin-4 is a new histological and serological tumor associated marker for breast cancer. (PMID: 17474988) Fabre-Lafay S … Lopez M (BMC cancer 2007) 3 4 22
  3. Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM-17. (PMID: 15784625) Fabre-Lafay S … Lopez M (The Journal of biological chemistry 2005) 3 4 22
  4. Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction. (PMID: 11544254) Reymond N … Lopez M (The Journal of biological chemistry 2001) 2 3 4
  5. Structure of measles virus hemagglutinin bound to its epithelial receptor nectin-4. (PMID: 23202587) Zhang X … Gao GF (Nature structural & molecular biology 2013) 3 4

Products for NECTIN4 Gene

  • Boster Bio Antibodies for NECTIN4
  • Boster Bio ELISA Kits for NECTIN4

Sources for NECTIN4 Gene