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NTN4 netrin 4 [ Homo sapiens (human) ]

Gene ID: 59277, updated on 5-Mar-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (95657807..95791155, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (95636970..95770314, complement)
105.20220307 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
  • 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. Netrin-4: Focus on Its Role in Axon Guidance, Tissue Stability, Angiogenesis and Tumors. Dong F, et al. Cell Mol Neurobiol, 2023 Jul. PMID 36350538
  2. NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer. Yi L, et al. Sci Rep, 2022 Jun 22. PMID 35732855, Free PMC Article
  3. Netrin-4 expression by human endothelial cells inhibits endothelial inflammation and senescence. Zhang H, et al. Int J Biochem Cell Biol, 2021 May. PMID 33636396
  4. eQTL Colocalization Analyses Identify NTN4 as a Candidate Breast Cancer Risk Gene. Beesley J, et al. Am J Hum Genet, 2020 Oct 1. PMID 32871102, Free PMC Article
  5. Enrichment of damaging missense variants in genes related with axonal guidance signalling in sporadic Meniere's disease. Gallego-Martinez A, et al. J Med Genet, 2020 Feb. PMID 31494579

See all (52) 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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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_2023_10

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

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