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    NECTIN4 nectin cell adhesion molecule 4 [ Homo sapiens (human) ]

    Gene ID: 81607, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NECTIN4provided by HGNC
    Official Full Name
    nectin cell adhesion molecule 4provided by HGNC
    Primary source
    HGNC:HGNC:19688
    See related
    Ensembl:ENSG00000143217 MIM:609607; AllianceGenome:HGNC:19688
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    LNIR; PRR4; EDSS1; PVRL4; nectin-4
    Summary
    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]
    Expression
    Biased expression in skin (RPKM 30.6), esophagus (RPKM 23.7) and 7 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NECTIN4 in Genome Data Viewer
    Location:
    1q23.3
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (161070998..161089558, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (160208489..160227037, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (161040788..161059348, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1971 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1972 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:161015335-161016534 Neighboring gene upstream transcription factor 1 Neighboring gene Rho GTPase activating protein 30 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161038974-161039520 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1974 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161044543-161045219 Neighboring gene NECTIN4 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1975 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1466 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1467 Neighboring gene kelch domain containing 9 Neighboring gene prefoldin subunit 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1976 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161087283-161088263

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Nectin-4: a new prognostic biomarker for efficient therapeutic targeting of primary and metastatic triple-negative breast cancer. M-Rabet M, et al. Ann Oncol, 2017 Apr 1. PMID 27998973
    2. Genetic variants in NECTIN4 encoding an adhesion molecule are associated with continued opioid use. Fang CP, et al. PLoS One, 2020. PMID 32555608, Free PMC Article
    3. Nectin-4 is a new histological and serological tumor associated marker for breast cancer. Fabre-Lafay S, et al. BMC Cancer, 2007 May 2. PMID 17474988, Free PMC Article
    4. Identification of nectin-4 oncoprotein as a diagnostic and therapeutic target for lung cancer. Takano A, et al. Cancer Res, 2009 Aug 15. PMID 19679554
    5. The Prognostic Role of Expression of Nectin-4 in Esophageal Cancer. Lin X, et al. Med Sci Monit, 2019 Dec 28. PMID 31883369, Free PMC Article

    See all (90) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A Specificity Protein 1 assists the Progression of the Papillary Thyroid Cell Line by Initiating NECTIN4.
      Title: A Specificity Protein 1 assists the Progression of the Papillary Thyroid Cell Line by Initiating NECTIN4.
    2. Molecular Crosstalk Between Adherens Junction Proteins, E-cadherin and Nectin-4.
      Title: Molecular Crosstalk Between Adherens Junction Proteins, E-cadherin and Nectin-4.
    3. Nectin cell adhesion molecule-4 (NECTIN-4): A potential target for cancer therapy.
      Title: Nectin cell adhesion molecule-4 (NECTIN-4): A potential target for cancer therapy.
    4. Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts.
      Title: Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts.
    5. Expression of PVRL4, a molecular target for cancer treatment, is transcriptionally regulated by FOS.
      Title: Expression of PVRL4, a molecular target for cancer treatment, is transcriptionally regulated by FOS.
    6. Nectin-4 regulates cellular senescence-associated enlargement of cell size.
      Title: Nectin-4 regulates cellular senescence-associated enlargement of cell size.
    7. A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family.
      Title: A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family.
    8. A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1.
      Title: A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1.
    9. Trop-2 and Nectin-4 immunohistochemical expression in metastatic colorectal cancer: searching for the right population for drugs' development.
      Title: Trop-2 and Nectin-4 immunohistochemical expression in metastatic colorectal cancer: searching for the right population for drugs' development.
    10. Immunohistochemical Analysis of HER2, EGFR, and Nectin-4 Expression in Upper Urinary Tract Urothelial Carcinoma.
      Title: Immunohistochemical Analysis of HER2, EGFR, and Nectin-4 Expression in Upper Urinary Tract Urothelial Carcinoma.
    Submit: New GeneRIF Correction See all GeneRIFs (71)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Ectodermal dysplasia-syndactyly syndrome 1
    MedGen: C3150807 OMIM: 613573 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • DKFZp686K05193

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables receptor ligand activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables virus receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in homophilic cell adhesion via plasma membrane adhesion molecules IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of natural killer cell mediated cytotoxicity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in symbiont entry into host cell IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in adherens junction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in adherens junction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular exosome HDA PubMed 
    is_active_in plasma membrane IC
    Inferred by Curator
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    nectin-4
    Names
    Ig superfamily receptor LNIR
    nectin 4
    poliovirus receptor-related 4
    poliovirus receptor-related protein 4

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_028109.1 RefSeqGene

      Range
      5038..23598
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_030916.3 → NP_112178.2  nectin-4 precursor

      See identical proteins and their annotated locations for NP_112178.2

      Status: REVIEWED

      Source sequence(s)
      BC010423, BC013892, CF529301, DB223835
      Consensus CDS
      CCDS1216.1
      UniProtKB/Swiss-Prot
      B4DQW3, Q96K15, Q96NY8
      UniProtKB/TrEMBL
      K4PZ75
      Related
      ENSP00000356991.3, ENST00000368012.4
      Conserved Domains (3) summary
      cd00096
      Location:266 → 329
      Ig; Immunoglobulin domain
      cd05888
      Location:38 → 146
      IgV_1_Nectin-4_like; First immunoglobulin (Ig) domain of nectin-4, and similar domains
      cd07704
      Location:149 → 242
      IgC1_2_Nectin-3-4_like; Second immunoglobulin (Ig) domain of nectin-3 and nectin-4 (poliovirus receptor related protein 4), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      161070998..161089558 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005245508.4 → XP_005245565.1  nectin-4 isoform X3

      See identical proteins and their annotated locations for XP_005245565.1

      Conserved Domains (3) summary
      cd05888
      Location:46 → 146
      Ig1_Nectin-4_like; Frst immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4, or as LNIR receptor) and similar proteins
      cd00096
      Location:266 → 329
      Ig; Immunoglobulin domain
      cd07704
      Location:149 → 242
      Ig2_Nectin-3-4_like; Second immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3), nectin-4 (poliovirus receptor related protein 4) and similar proteins

    2. XM_047431288.1 → XP_047287244.1  nectin-4 isoform X4

    3. XM_011510022.3 → XP_011508324.1  nectin-4 isoform X2

      Conserved Domains (4) summary
      cd05888
      Location:46 → 146
      Ig1_Nectin-4_like; Frst immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4, or as LNIR receptor) and similar proteins
      cd07704
      Location:149 → 242
      Ig2_Nectin-3-4_like; Second immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3), nectin-4 (poliovirus receptor related protein 4) and similar proteins
      smart00408
      Location:268 → 320
      IGc2; Immunoglobulin C-2 Type
      smart00410
      Location:259 → 332
      IG_like; Immunoglobulin like

    4. XM_011510021.3 → XP_011508323.1  nectin-4 isoform X1

      See identical proteins and their annotated locations for XP_011508323.1

      Conserved Domains (4) summary
      cd05888
      Location:46 → 146
      Ig1_Nectin-4_like; Frst immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4, or as LNIR receptor) and similar proteins
      cd07704
      Location:149 → 242
      Ig2_Nectin-3-4_like; Second immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3), nectin-4 (poliovirus receptor related protein 4) and similar proteins
      smart00408
      Location:268 → 320
      IGc2; Immunoglobulin C-2 Type
      smart00410
      Location:259 → 332
      IG_like; Immunoglobulin like

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      160208489..160227037 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054338911.1 → XP_054194886.1  nectin-4 isoform X3

    2. XM_054338912.1 → XP_054194887.1  nectin-4 isoform X4

    3. XM_054338910.1 → XP_054194885.1  nectin-4 isoform X2

    4. XM_054338909.1 → XP_054194884.1  nectin-4 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96NY8.1 GenPept UniProtKB/Swiss-Prot:Q96NY8

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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