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    NRG4 neuregulin 4 [ Homo sapiens (human) ]

    Gene ID: 145957, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NRG4provided by HGNC
    Official Full Name
    neuregulin 4provided by HGNC
    Primary source
    HGNC:HGNC:29862
    See related
    Ensembl:ENSG00000169752 MIM:610894; AllianceGenome:HGNC:29862
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HRG4
    Summary
    The neuregulins, including NRG4, activate type-1 growth factor receptors (see EGFR; MIM 131550) to initiating cell-to-cell signaling through tyrosine phosphorylation (Harari et al., 1999 [PubMed 10348342]).[supplied by OMIM, Mar 2008]
    Expression
    Ubiquitous expression in prostate (RPKM 2.0), skin (RPKM 1.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NRG4 in Genome Data Viewer
    Location:
    15q24.2
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (75935393..76060240, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (73806132..73930956, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (76233277..76304765, complement)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:76084438-76084938 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:76084939-76085439 Neighboring gene dynamin 1 pseudogene 49 Neighboring gene Sharpr-MPRA regulatory region 8353 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6682 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6683 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:76135870-76136767 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:76163679-76164628 Neighboring gene ubiquitin conjugating enzyme E2 Q2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:76195387-76196046 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:76196047-76196704 Neighboring gene RNA, 7SL, cytoplasmic 510, pseudogene Neighboring gene F-box protein 22 Neighboring gene uncharacterized LOC124903616 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:76311273-76311774 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9868 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9869 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9870 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6687 Neighboring gene transmembrane protein 266 Neighboring gene uncharacterized LOC124903531 Neighboring gene Sharpr-MPRA regulatory region 3592 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:76432149-76432982 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:76442422-76442685 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:76442959-76443537 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9873 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:76444006-76444636 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:76453363-76454200 Neighboring gene uncharacterized LOC101929439

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. The brown fat-secreted adipokine neuregulin 4 is decreased in human and murine chronic kidney disease. Kralisch S, et al. Eur J Endocrinol, 2019 Aug. PMID 31153139
    2. A case-control study: Association between serum neuregulin 4 level and non-alcoholic fatty liver disease. Dai YN, et al. Metabolism, 2015 Dec. PMID 26476959
    3. Comparison of serum Neuregulin 4 (Nrg4) levels in adults with newly diagnosed type 2 diabetes mellitus and controls without diabetes. Kang YE, et al. Diabetes Res Clin Pract, 2016 Jul. PMID 27329015
    4. Circulating neuregulin 4 levels are inversely associated with subclinical cardiovascular disease in obese adults. Jiang J, et al. Sci Rep, 2016 Nov 7. PMID 27819316, Free PMC Article
    5. Elevated circulating Neuregulin4 level in patients with diabetes. Chen LL, et al. Diabetes Metab Res Rev, 2017 May. PMID 27862843

    See all (39) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Neuregulin 4 (Nrg4) cooperates with melatonin to regulate the PRL expression via ErbB4/Erk signaling pathway as a potential prolactin (PRL) regulator.
      Title: Neuregulin 4 (Nrg4) cooperates with melatonin to regulate the PRL expression via ErbB4/Erk signaling pathway as a potential prolactin (PRL) regulator.
    2. NGR4 and ERBB4 as Promising Diagnostic and Therapeutic Targets for Metabolic Disorders.
      Title: NGR4 and ERBB4 as Promising Diagnostic and Therapeutic Targets for Metabolic Disorders.
    3. Neuregulin 4 (NRG4) - the hormone with clinical significance in gestational diabetes mellitus.
      Title: Neuregulin 4 (NRG4) - the hormone with clinical significance in gestational diabetes mellitus.
    4. Negative Correlation between Neuregulin-4 and IL-9 Serum Levels in Patients with Coronary Artery Disease.
      Title: Negative Correlation between Neuregulin-4 and IL-9 Serum Levels in Patients with Coronary Artery Disease.
    5. Mutations of NRG4 Contribute to the Pathogenesis of Nonalcoholic Fatty Liver Disease and Related Metabolic Disorders.
      Title: Mutations of NRG4 Contribute to the Pathogenesis of Nonalcoholic Fatty Liver Disease and Related Metabolic Disorders.
    6. Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease?
      Title: Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease?
    7. Serum neuregulin 4 (NRG-4) level and non-alcoholic fatty liver disease (NAFLD): A case-control study.
      Title: Serum neuregulin 4 (NRG-4) level and non-alcoholic fatty liver disease (NAFLD): A case-control study.
    8. Study findings suggested circulating NRG4 may play a role in in the development of diabetes mellitus in cross-sectional studies and circulating NRG4 might be associated with imbalance in glucose metabolism and obesity.[meta-analysis]
      Title: Association between circulating neuregulin4 levels and diabetes mellitus: A meta-analysis of observational studies.
    9. Nrg-4 levels may be a good predictor of early detection of one or more diabetic microvascular complicationss
      Title: Is Neuregulin-4 a predictive marker of microvascular complications in type 2 diabetes mellitus?
    10. These findings together suggested that circulating Nrg4 levels were reduced in diabetic peripheral neuropathy patients and Nrg4 may be a novel adipokine associated with inflammation, oxidative stress, and long-term glycemic control in nT2DM patients.
      Title: Decreased plasma neuregulin 4 levels are associated with peripheral neuropathy in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study.
    Submit: New GeneRIF Correction See all GeneRIFs (29)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
    EBI GWAS Catalog
    Seventy-five genetic loci influencing the human red blood cell.
    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)

    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

    • DKFZp779N0541, DKFZp779N1944

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables growth factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables receptor ligand activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in ERBB4-ERBB4 signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular space IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    pro-neuregulin-4, membrane-bound isoform
    Names
    heregulin 4
    pro-NRG4

    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.

    mRNA and Protein(s)

    1. NM_138573.4 → NP_612640.1  pro-neuregulin-4, membrane-bound isoform

      See identical proteins and their annotated locations for NP_612640.1

      Status: VALIDATED

      Source sequence(s)
      AC027104, BC017568
      Consensus CDS
      CCDS10288.1
      UniProtKB/Swiss-Prot
      A6NIE8, Q8WWG1
      UniProtKB/TrEMBL
      H3BP63
      Related
      ENSP00000378367.3, ENST00000394907.8
      Conserved Domains (1) summary
      cl28647
      Location:9 → 83
      PHA02887; EGF-like protein; Provisional

    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_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      75935393..76060240 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047432183.1 → XP_047288139.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    2. XM_047432182.1 → XP_047288138.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63
      Related
      ENSP00000455167.1, ENST00000563910.5

    3. XM_047432181.1 → XP_047288137.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    4. XM_047432184.1 → XP_047288140.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    5. XM_047432178.1 → XP_047288134.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    6. XM_047432179.1 → XP_047288135.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    7. XM_047432180.1 → XP_047288136.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    8. XM_017021948.3 → XP_016877437.1  pro-neuregulin-4, membrane-bound isoform isoform X2

      UniProtKB/Swiss-Prot
      A6NIE8, Q8WWG1
      UniProtKB/TrEMBL
      H3BP63
      Conserved Domains (1) summary
      cl28647
      Location:9 → 83
      PHA02887; EGF-like protein; Provisional

    9. XM_024449848.2 → XP_024305616.1  pro-neuregulin-4, membrane-bound isoform isoform X2

      UniProtKB/Swiss-Prot
      A6NIE8, Q8WWG1
      UniProtKB/TrEMBL
      H3BP63
      Related
      ENSP00000457335.1, ENST00000566417.5
      Conserved Domains (1) summary
      cl28647
      Location:9 → 83
      PHA02887; EGF-like protein; Provisional

    10. XM_047432185.1 → XP_047288141.1  pro-neuregulin-4, membrane-bound isoform isoform X2

      UniProtKB/Swiss-Prot
      A6NIE8, Q8WWG1
      UniProtKB/TrEMBL
      H3BP63

    11. XM_047432186.1 → XP_047288142.1  pro-neuregulin-4, membrane-bound isoform isoform X2

      UniProtKB/Swiss-Prot
      A6NIE8, Q8WWG1
      UniProtKB/TrEMBL
      H3BP63

    RNA

    1. XR_007064433.1 RNA Sequence

    2. XR_007064432.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      73806132..73930956 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054377346.1 → XP_054233321.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    2. XM_054377345.1 → XP_054233320.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    3. XM_054377344.1 → XP_054233319.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    4. XM_054377347.1 → XP_054233322.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    5. XM_054377342.1 → XP_054233317.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    6. XM_054377343.1 → XP_054233318.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    7. XM_054377341.1 → XP_054233316.1  pro-neuregulin-4, membrane-bound isoform isoform X1

      UniProtKB/TrEMBL
      H3BP63

    8. XM_054377351.1 → XP_054233326.1  pro-neuregulin-4, membrane-bound isoform isoform X2

      UniProtKB/Swiss-Prot
      A6NIE8, Q8WWG1
      UniProtKB/TrEMBL
      H3BP63

    9. XM_054377350.1 → XP_054233325.1  pro-neuregulin-4, membrane-bound isoform isoform X2

      UniProtKB/Swiss-Prot
      A6NIE8, Q8WWG1
      UniProtKB/TrEMBL
      H3BP63

    10. XM_054377348.1 → XP_054233323.1  pro-neuregulin-4, membrane-bound isoform isoform X2

      UniProtKB/Swiss-Prot
      A6NIE8, Q8WWG1
      UniProtKB/TrEMBL
      H3BP63

    11. XM_054377349.1 → XP_054233324.1  pro-neuregulin-4, membrane-bound isoform isoform X2

      UniProtKB/Swiss-Prot
      A6NIE8, Q8WWG1
      UniProtKB/TrEMBL
      H3BP63

    RNA

    1. XR_008488924.1 RNA Sequence

    2. XR_008488923.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8WWG1.1 GenPept UniProtKB/Swiss-Prot:Q8WWG1

    Gene LinkOut

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

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