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Aliases for NRG4 Gene

Aliases for NRG4 Gene

  • Neuregulin 4 2 3 5
  • Pro-NRG4 3 4
  • Pro-Neuregulin-4, Membrane-Bound Isoform 3
  • Heregulin 4 3
  • HRG4 3

External Ids for NRG4 Gene

Previous GeneCards Identifiers for NRG4 Gene

  • GC15M074022
  • GC15M076233
  • GC15M052990

Summaries for NRG4 Gene

Entrez Gene Summary for NRG4 Gene

  • 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]

GeneCards Summary for NRG4 Gene

NRG4 (Neuregulin 4) is a Protein Coding gene. Among its related pathways are RET signaling and Cytokine Signaling in Immune system. Gene Ontology (GO) annotations related to this gene include receptor binding and growth factor activity.

UniProtKB/Swiss-Prot for NRG4 Gene

  • Low affinity ligand for the ERBB4 tyrosine kinase receptor. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. Does not bind to the ERBB1, ERBB2 and ERBB3 receptors (By similarity).

Gene Wiki entry for NRG4 Gene

Additional gene information for NRG4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NRG4 Gene

Genomics for NRG4 Gene

GeneHancer (GH) Regulatory Elements for NRG4 Gene

Promoters and enhancers for NRG4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH15I076059 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE 571.5 -0.1 -130 1.4 PKNOX1 KLF17 ZNF76 SIN3A FEZF1 ZNF335 GLIS2 SCRT2 ZNF391 ETV6 NRG4 TMEM266 LOC441728 DNM1P35 LOC101929439
GH15I076011 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE 550.2 +47.5 47518 1.4 HDAC1 PKNOX1 ARNT RFX5 ZNF335 EGR1 EGR2 RXRA USF2 REST NRG4 FBXO22 MIR631 MAN2C1 GC15M075978
GH15I076058 Enhancer 0.7 ENCODE 550.8 +0.8 750 0.1 CTCF PKNOX1 SUZ12 MAX SIN3A RAD21 ZNF335 ZNF600 RUNX3 ZBTB20 NRG4 TMEM266 LOC441728 DNM1P35 GC15M075978
GH15I075901 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 18.3 +156.7 156677 3.8 DMAP1 YY1 ZNF213 E2F8 ZNF143 SP3 MEF2D ZNF610 GLIS1 NBN FBXO22 DNM1P35 NRG4 SIN3A MAN2C1 ENSG00000260274 ENSG00000203392 UBE2Q2 RN7SL510P
GH15I075890 Enhancer 0.8 Ensembl ENCODE 18.3 +168.1 168071 2.3 SMARCE1 JUN CEBPB CEBPG FOSL1 JUND SMARCA4 POLR2A CEBPA HMBOX1 FBXO22 NRG4 MIR631 RN7SL510P UBE2Q2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around NRG4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the NRG4 gene promoter:

Genomic Locations for NRG4 Gene

Genomic Locations for NRG4 Gene
chr15:75,935,969-76,059,795
(GRCh38/hg38)
Size:
123,827 bases
Orientation:
Minus strand
chr15:76,228,310-76,352,136
(GRCh37/hg19)

Genomic View for NRG4 Gene

Genes around NRG4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NRG4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NRG4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NRG4 Gene

Proteins for NRG4 Gene

  • Protein details for NRG4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WWG1-NRG4_HUMAN
    Recommended name:
    Pro-neuregulin-4, membrane-bound isoform
    Protein Accession:
    Q8WWG1
    Secondary Accessions:
    • A6NIE8

    Protein attributes for NRG4 Gene

    Size:
    115 amino acids
    Molecular mass:
    12722 Da
    Quaternary structure:
    • Interacts with ERBB4.

neXtProt entry for NRG4 Gene

Post-translational modifications for NRG4 Gene

  • Extensive glycosylation precedes the proteolytic cleavage.
  • Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.
  • Glycosylation at isoforms=39

No data available for DME Specific Peptides for NRG4 Gene

Domains & Families for NRG4 Gene

Gene Families for NRG4 Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins

Protein Domains for NRG4 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for NRG4 Gene

Graphical View of Domain Structure for InterPro Entry

Q8WWG1

UniProtKB/Swiss-Prot:

NRG4_HUMAN :
  • The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization (By similarity).
  • Belongs to the neuregulin family.
Domain:
  • The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization (By similarity).
  • ERBB receptor binding is elicited entirely by the EGF-like domain.
Family:
  • Belongs to the neuregulin family.
genes like me logo Genes that share domains with NRG4: view

Function for NRG4 Gene

Molecular function for NRG4 Gene

UniProtKB/Swiss-Prot Function:
Low affinity ligand for the ERBB4 tyrosine kinase receptor. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. Does not bind to the ERBB1, ERBB2 and ERBB3 receptors (By similarity).

Phenotypes From GWAS Catalog for NRG4 Gene

Gene Ontology (GO) - Molecular Function for NRG4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004713 protein tyrosine kinase activity TAS --
GO:0005088 Ras guanyl-nucleotide exchange factor activity TAS --
GO:0005102 receptor binding IBA --
GO:0005515 protein binding IPI 21516116
GO:0008083 growth factor activity IEA --
genes like me logo Genes that share ontologies with NRG4: view

Phenotypes for NRG4 Gene

MGI mutant phenotypes for NRG4:
inferred from 1 alleles
GenomeRNAi human phenotypes for NRG4:
genes like me logo Genes that share phenotypes with NRG4: view

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for NRG4 Gene

Localization for NRG4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NRG4 Gene

Pro-neuregulin-4, membrane-bound isoform: Cell membrane; Single-pass type I membrane protein. Note=Does not seem to be active. {ECO:0000250}.
Neuregulin-4: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NRG4 gene
Compartment Confidence
plasma membrane 4
extracellular 4
mitochondrion 1

Gene Ontology (GO) - Cellular Components for NRG4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA --
GO:0005622 intracellular IEA --
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with NRG4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for NRG4 Gene

Pathways & Interactions for NRG4 Gene

SuperPathway Contained pathways
1 RET signaling
2 Signaling by ERBB2
3 PI3K/AKT activation
4 Signaling by ERBB4
5 ErbB signaling pathway
genes like me logo Genes that share pathways with NRG4: view

Pathways by source for NRG4 Gene

SIGNOR curated interactions for NRG4 Gene

Activates:

Gene Ontology (GO) - Biological Process for NRG4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0010469 regulation of receptor activity IEA --
GO:0018108 peptidyl-tyrosine phosphorylation IEA --
GO:0035556 intracellular signal transduction IBA --
GO:0038128 ERBB2 signaling pathway TAS --
genes like me logo Genes that share ontologies with NRG4: view

Drugs & Compounds for NRG4 Gene

(1) Drugs for NRG4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with NRG4: view

Transcripts for NRG4 Gene

Unigene Clusters for NRG4 Gene

Neuregulin 4:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NRG4 Gene

No ASD Table

Relevant External Links for NRG4 Gene

GeneLoc Exon Structure for
NRG4
ECgene alternative splicing isoforms for
NRG4

Expression for NRG4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for NRG4 Gene

mRNA differential expression in normal tissues according to GTEx for NRG4 Gene

This gene is overexpressed in Brain - Cerebellar Hemisphere (x6.2), Brain - Cerebellum (x5.3), and Pancreas (x4.2).

NURSA nuclear receptor signaling pathways regulating expression of NRG4 Gene:

NRG4

SOURCE GeneReport for Unigene cluster for NRG4 Gene:

Hs.732438

Evidence on tissue expression from TISSUES for NRG4 Gene

  • Liver(4.3)
  • Nervous system(2.4)
genes like me logo Genes that share expression patterns with NRG4: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for NRG4 Gene

Orthologs for NRG4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NRG4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NRG4 33 34
  • 98.84 (n)
cow
(Bos Taurus)
Mammalia NRG4 33
  • 87.83 (n)
rat
(Rattus norvegicus)
Mammalia Nrg4 33
  • 84.64 (n)
mouse
(Mus musculus)
Mammalia Nrg4 33 16 34
  • 82.61 (n)
dog
(Canis familiaris)
Mammalia NRG4 34
  • 77 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NRG4 34
  • 67 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NRG4 34
  • 41 (a)
OneToOne
chicken
(Gallus gallus)
Aves NRG4 33 34
  • 69.44 (n)
Species where no ortholog for NRG4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for NRG4 Gene

ENSEMBL:
Gene Tree for NRG4 (if available)
TreeFam:
Gene Tree for NRG4 (if available)

Paralogs for NRG4 Gene

genes like me logo Genes that share paralogs with NRG4: view

No data available for Paralogs for NRG4 Gene

Variants for NRG4 Gene

Sequence variations from dbSNP and Humsavar for NRG4 Gene

SNP ID Clin Chr 15 pos Variation AA Info Type
rs1000007596 -- 75,993,197(-) G/A intron_variant
rs1000053820 -- 76,054,500(-) C/T genic_upstream_transcript_variant, intron_variant
rs1000077660 -- 76,046,822(-) C/T genic_upstream_transcript_variant, intron_variant
rs1000102404 -- 75,978,042(-) C/G intron_variant
rs1000105070 -- 75,992,848(-) T/G intron_variant

Structural Variations from Database of Genomic Variants (DGV) for NRG4 Gene

Variant ID Type Subtype PubMed ID
dgv2622n100 CNV gain 25217958
esv2749895 CNV deletion 23290073
esv2749898 CNV deletion 23290073
esv2749900 CNV deletion 23290073
esv3636933 CNV gain 21293372
nsv1108966 CNV deletion 24896259
nsv1116463 OTHER inversion 24896259
nsv518214 CNV loss 19592680
nsv518261 CNV loss 19592680
nsv569998 CNV gain 21841781

Variation tolerance for NRG4 Gene

Residual Variation Intolerance Score: 44.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.74; 33.04% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NRG4 Gene

Human Gene Mutation Database (HGMD)
NRG4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NRG4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NRG4 Gene

Disorders for NRG4 Gene

Additional Disease Information for NRG4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for NRG4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for NRG4 Gene

Publications for NRG4 Gene

  1. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 44 58
  2. Characterization of the cell membrane-associated products of the Neuregulin 4 gene. (PMID: 17684490) Hayes NV … Gullick WJ (Oncogene 2008) 3 22 58
  3. Identification and characterization of novel spliced variants of neuregulin 4 in prostate cancer. (PMID: 17545517) Hayes NV … Gullick WJ (Clinical cancer research : an official journal of the American Association for Cancer Research 2007) 3 22 58
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 58
  5. Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients. (PMID: 15583696) Memon AA … Nexo E (British journal of cancer 2004) 3 22 58

Products for NRG4 Gene

Sources for NRG4 Gene

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