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NRG4 neuregulin 4 [ Homo sapiens (human) ]

Gene ID: 145957, updated on 3-Apr-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
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Genomic context

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Location:
15q24.2
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (75935393..76060240, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (73806132..73930956, complement)
105.20220307 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: 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. Neuregulin 4 (NRG4) - the hormone with clinical significance in gestational diabetes mellitus. Attique H, et al. J Obstet Gynaecol, 2022 Aug. PMID 35603674
  2. Mutations of NRG4 Contribute to the Pathogenesis of Nonalcoholic Fatty Liver Disease and Related Metabolic Disorders. Li Y, et al. Diabetes, 2021 Oct. PMID 34261740
  3. Serum neuregulin 4 (NRG-4) level and non-alcoholic fatty liver disease (NAFLD): A case-control study. Tutunchi H, et al. Int J Clin Pract, 2021 Oct. PMID 34159710
  4. Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease? De Munck TJI, et al. PLoS One, 2021. PMID 33989346, Free PMC Article
  5. Is Neuregulin-4 a predictive marker of microvascular complications in type 2 diabetes mellitus? Kocak MZ, et al. Eur J Clin Invest, 2020 Mar. PMID 31999832

See all (38) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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?
  6. 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.
  7. 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.
  8. 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?
  9. 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.
  10. Median serum NRG4 was significantly lower in patients with end-stage kidney disease.
    Title: The brown fat-secreted adipokine neuregulin 4 is decreased in human and murine chronic kidney disease.
Submit: New GeneRIF Correction See all GeneRIFs (28)

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
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)

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

  • 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_2023_10

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

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

    Related
    ENSP00000455167.1, ENST00000563910.5

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

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

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

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

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

  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

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

    UniProtKB/Swiss-Prot
    A6NIE8, Q8WWG1

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

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

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

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

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

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

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

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

    UniProtKB/Swiss-Prot
    A6NIE8, Q8WWG1

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

    UniProtKB/Swiss-Prot
    A6NIE8, Q8WWG1

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

    UniProtKB/Swiss-Prot
    A6NIE8, Q8WWG1

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

    UniProtKB/Swiss-Prot
    A6NIE8, Q8WWG1

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

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