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    NTN4 netrin 4 [ Homo sapiens (human) ]

    Gene ID: 59277, updated on 2-Nov-2024

    Summary

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    Official Symbol
    NTN4provided by HGNC
    Official Full Name
    netrin 4provided by HGNC
    Primary source
    HGNC:HGNC:13658
    See related
    Ensembl:ENSG00000074527 MIM:610401; AllianceGenome:HGNC:13658
    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
    PRO3091
    Summary
    This gene encodes a member of the netrin family of proteins, which function in various biological processes including axon guidance, tumorogenesis, and angiogenesis. Netrins are laminin-related proteins that have an N-terminal laminin-type domain, epidermal growth factor-like repeat domain, and a positively charged heparin-binding domain at the C-terminus. The protein encoded by this gene is involved in processes including neurite growth and migration, angiogenesis and mural cell adhesion to endothelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]
    Expression
    Broad expression in spleen (RPKM 88.7), kidney (RPKM 62.7) and 20 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NTN4 in Genome Data Viewer
    Location:
    12q22
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (95657807..95791155, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (95636970..95770314, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (96051583..96184933, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6810 Neighboring gene methionyl aminopeptidase 2 Neighboring gene MPRA-validated peak1899 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:95916458-95916958 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:95936387-95936886 Neighboring gene ubiquitin specific peptidase 44 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6811 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:96004940-96005508 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr12:96005509-96006077 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:96008766-96009393 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:96016523-96017477 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4739 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:96026735-96027934 Neighboring gene Sharpr-MPRA regulatory region 15569 Neighboring gene phosphoglycerate mutase 1 pseudogene 5 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:96087614-96088118 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:96088119-96088623 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6812 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6813 Neighboring gene uncharacterized LOC105369919 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:96125327-96125544 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6815 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 12:96134654 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 12:96141252 Neighboring gene RNA, U6 small nuclear 247, pseudogene Neighboring gene SNRPF divergent transcript Neighboring gene long intergenic non-protein coding RNA 2410

    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 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. RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression. Wu Z, et al. Oncol Rep, 2023 Nov. PMID 37800632, Free PMC Article
    2. Inhibition of human placental endothelial cell proliferation and angiogenesis by netrin-4. Dakouane-Giudicelli M, et al. Placenta, 2015 Nov. PMID 26390805
    3. Netrin-4 regulates thalamocortical axon branching in an activity-dependent fashion. Hayano Y, et al. Proc Natl Acad Sci U S A, 2014 Oct 21. PMID 25288737, Free PMC Article
    4. NTN4 is associated with breast cancer metastasis via regulation of EMT-related biomarkers. Xu X, et al. Oncol Rep, 2017 Jan. PMID 27840993
    5. NETRIN-4 protects glioblastoma cells FROM temozolomide induced senescence. Li L, et al. PLoS One, 2013. PMID 24265816, Free PMC Article

    See all (55) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Hepatic Expression of NTN4 and Its Receptors in Patients with Hepatocellular Carcinoma.
      Title: Hepatic Expression of NTN4 and Its Receptors in Patients with Hepatocellular Carcinoma.
    2. RNA-binding protein quaking 5 inhibits the progression of non-small cell lung cancer by upregulating netrin-4 expression.
      Title: RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression.
    3. Netrin-4: Focus on Its Role in Axon Guidance, Tissue Stability, Angiogenesis and Tumors.
      Title: Netrin-4: Focus on Its Role in Axon Guidance, Tissue Stability, Angiogenesis and Tumors.
    4. NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer.
      Title: NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer.
    5. The Interaction of NTN4 and miR-17-92 Polymorphisms on Breast Cancer Susceptibility in a Chinese Population.
      Title: The Interaction of NTN4 and miR-17-92 Polymorphisms on Breast Cancer Susceptibility in a Chinese Population.
    6. Netrin-4 expression by human endothelial cells inhibits endothelial inflammation and senescence.
      Title: Netrin-4 expression by human endothelial cells inhibits endothelial inflammation and senescence.
    7. Anti-Inflammatory Role of Netrin-4 in Diabetic Retinopathy.
      Title: Anti-Inflammatory Role of Netrin-4 in Diabetic Retinopathy.
    8. Enrichment of damaging missense variants in genes related with axonal guidance signalling in sporadic Meniere's disease.
      Title: Enrichment of damaging missense variants in genes related with axonal guidance signalling in sporadic Meniere's disease.
    9. eQTL Colocalization Analyses Identify NTN4 as a Candidate Breast Cancer Risk Gene.
      Title: eQTL Colocalization Analyses Identify NTN4 as a Candidate Breast Cancer Risk Gene.
    10. Findings indicate that activation of notch receptor 1 (Notch1) signalling significantly up-regulated Netrin4 (NTN4) mRNA and protein expressions.
      Title: Notch1 activates angiogenic regulator Netrin4 in endothelial cells.
    Submit: New GeneRIF Correction See all GeneRIFs (35)

    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

    EBI GWAS Catalog

    Description
    A genome-wide association study in Koreans identifies susceptibility loci for allergic nickel dermatitis.
    EBI GWAS Catalog
    Genome-wide association studies identify four ER negative-specific breast cancer risk loci.
    EBI GWAS Catalog
    Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    • FLJ23180

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables laminin-1 binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in animal organ morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in axon guidance IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in basement membrane assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cell migration IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in neuron remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of branching involved in salivary gland morphogenesis by extracellular matrix-epithelial cell signaling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in substrate adhesion-dependent cell spreading IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in tissue development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of laminin complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    netrin-4
    Names
    beta-netrin
    hepar-derived netrin-like protein

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_051252.1 RefSeqGene

      Range
      5443..138400
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001329700.2 → NP_001316629.1  netrin-4 isoform 2 precursor

      Status: REVIEWED

      Source sequence(s)
      AK290591, AK315796, AL137540, AY330211, BI549738, DB473670
      Consensus CDS
      CCDS86325.1
      UniProtKB/TrEMBL
      B2RE43
      Related
      ENSP00000447292.1, ENST00000553059.1
      Conserved Domains (5) summary
      smart00180
      Location:395 → 446
      EGF_Lam; Laminin-type epidermal growth factor-like domai
      cd00055
      Location:261 → 320
      EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...
      pfam00053
      Location:332 → 392
      Laminin_EGF; Laminin EGF domain
      pfam00055
      Location:43 → 260
      Laminin_N; Laminin N-terminal (Domain VI)
      cl02512
      Location:504 → 603
      NTR_like; NTR_like domain; a beta barrel with an oligosaccharide/oligonucleotide-binding fold found in netrins, complement proteins, tissue inhibitors of metalloproteases (TIMP), and procollagen C-proteinase enhancers (PCOLCE), amongst others. In netrins, the ...

    2. NM_001329701.2 → NP_001316630.1  netrin-4 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AF297711, AK290591, AL137540, BP232567
      Consensus CDS
      CCDS86324.1
      UniProtKB/TrEMBL
      A8K3H6
      Related
      ENSP00000444432.1, ENST00000538383.5

    3. NM_001329702.2 → NP_001316631.1  netrin-4 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC008128, AC090001, AL137540
      Consensus CDS
      CCDS86324.1
      UniProtKB/TrEMBL
      A8K3H6

    4. NM_021229.4 → NP_067052.2  netrin-4 isoform 1 precursor

      See identical proteins and their annotated locations for NP_067052.2

      Status: REVIEWED

      Source sequence(s)
      AC090001, AF297711, AL833767, BC013591, BI549738
      Consensus CDS
      CCDS9054.1
      UniProtKB/Swiss-Prot
      B2RNC2, Q658K9, Q7L3F1, Q7L9D6, Q7Z5B6, Q9BZP1, Q9HB63, Q9NT44, Q9P133
      UniProtKB/TrEMBL
      B2RE43
      Related
      ENSP00000340998.4, ENST00000343702.9
      Conserved Domains (5) summary
      smart00180
      Location:395 → 446
      EGF_Lam; Laminin-type epidermal growth factor-like domai
      cd00055
      Location:261 → 320
      EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...
      cd03578
      Location:516 → 626
      NTR_netrin-4_like; NTR domain, Netrin-4-like subfamily; composed of the C-terminal NTR domains of netrin-4 (beta netrin) and similar proteins. Netrins are secreted proteins that function as tropic cues in the direction of axon growth and cell migration during neural ...
      pfam00053
      Location:332 → 392
      Laminin_EGF; Laminin EGF domain
      pfam00055
      Location:43 → 260
      Laminin_N; Laminin N-terminal (Domain VI)

    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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      95657807..95791155 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      95636970..95770314 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9HB63.2 GenPept UniProtKB/Swiss-Prot:Q9HB63

    Gene LinkOut

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

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