Free for academic non-profit institutions. Other users need a Commercial license

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 Immune System. 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

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

Genomics for NRG4 Gene

Regulatory Elements for NRG4 Gene

Enhancers for NRG4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH15F076059 0.6 ENCODE 21.5 -0.1 -131 1.4 PKNOX1 TBL1XR1 ZNF76 KLF17 FEZF1 RAD21 GLIS2 SCRT2 ZNF391 CREM NRG4 DNM1P35 TMEM266 LOC101929439
GH15F075901 0.2 ENCODE 18.2 +156.7 156743 3.6 HDGF PKNOX1 CREB3L1 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 ZNF143 FBXO22 ENSG00000260274 ENSG00000203392 NRG4 SNX33 DNM1P49 LOC441728 LOC105370902 ENSG00000261232 DNM1P35
GH15F075890 0.6 Ensembl ENCODE 18.2 +168.1 168072 2.3 PKNOX1 TAF1 JUN CEBPB CEBPG ZIC2 ZNF843 OSR2 JUND SMARCA4 FBXO22 NRG4 MIR631 RN7SL510P UBE2Q2
GH15F076139 1 Ensembl ENCODE 11.9 -80.1 -80056 1.5 CTCF ZNF362 ZNF654 TRIM22 REST RAD21 ZFP69B JUND KLF16 ZNF692 NRG4 TMEM266 LOC101929439
GH15F076147 0.8 Ensembl 11.2 -88.4 -88366 0.5 CTCF MAX SIN3A ZIC2 RAD21 ZFHX2 ZNF366 PATZ1 ZNF143 SMC3 NRG4 TMEM266 LOC101929439
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around NRG4 on UCSC Golden Path with GeneCards custom track

Promoters for NRG4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001796976 -5 1601 PKNOX1 TBL1XR1 KLF17 FEZF1 RAD21 GLIS2 SCRT2 ZNF391 CREM EGR2

Genomic Location for NRG4 Gene

Chromosome:
15
Start:
75,935,969 bp from pter
End:
76,059,795 bp from pter
Size:
123,827 bases
Orientation:
Minus strand

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 Asn 39

No data available for DME Specific Peptides for NRG4 Gene

Domains & Families for NRG4 Gene

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.
  • Contains 1 EGF-like domain.
Family:
  • Belongs to the neuregulin family.
genes like me logo Genes that share domains with NRG4: view

No data available for Gene Families for NRG4 Gene

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).

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

Animal Model Products

  • Taconic Biosciences Mouse Models for NRG4

Inhibitory RNA Products

Clone Products

Flow Cytometry 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
Jensen Localization Image for NRG4 Gene COMPARTMENTS Subcellular localization image for NRG4 gene
Compartment Confidence
extracellular 4
plasma membrane 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

Pathways & Interactions for NRG4 Gene

SuperPathways for NRG4 Gene

SuperPathway Contained pathways
1 RET signaling
2 GAB1 signalosome
3 Signaling by ERBB2
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:0014066 regulation of phosphatidylinositol 3-kinase signaling TAS --
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:

Inhibitory RNA Products

Clone Products

Flow Cytometry 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 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
genes like me logo Genes that share expression patterns with NRG4: view

Primer Products

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt 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 34 35
  • 98.84 (n)
cow
(Bos Taurus)
Mammalia NRG4 34
  • 87.83 (n)
rat
(Rattus norvegicus)
Mammalia Nrg4 34
  • 84.64 (n)
mouse
(Mus musculus)
Mammalia Nrg4 34 16 35
  • 82.61 (n)
dog
(Canis familiaris)
Mammalia NRG4 35
  • 77 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NRG4 35
  • 67 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NRG4 35
  • 41 (a)
OneToOne
chicken
(Gallus gallus)
Aves NRG4 34 35
  • 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 Sequence Context AA Info Type
rs10152136 -- 75,959,619(+) cttcc(C/T)gagta intron-variant
rs10152476 -- 75,961,157(+) TGAGA(C/G)TTATG intron-variant
rs10152481 -- 75,977,063(+) ggtac(C/T)gccgc intron-variant
rs10152491 -- 75,977,172(+) tcccc(A/C)aacca intron-variant
rs10152533 -- 75,976,933(+) acagc(A/T)gccct 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)

Relevant External Links for NRG4 Gene

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

Relevant External Links for NRG4

Genetic Association Database (GAD)
NRG4
Human Genome Epidemiology (HuGE) Navigator
NRG4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NRG4

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 S.D. … Anand S. (Diabetes Care 2010) 3 46 64
  2. Characterization of the cell membrane-associated products of the Neuregulin 4 gene. (PMID: 17684490) Hayes N.V. … Gullick W.J. (Oncogene 2008) 3 22 64
  3. Identification and characterization of novel spliced variants of neuregulin 4 in prostate cancer. (PMID: 17545517) Hayes N.V. … Gullick W.J. (Clin. Cancer Res. 2007) 3 22 64
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard D.S. … Malek J. (Genome Res. 2004) 3 4 64
  5. Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients. (PMID: 15583696) Memon A.A. … Nexo E. (Br. J. Cancer 2004) 3 22 64

Products for NRG4 Gene

Sources for NRG4 Gene

Content
Loading form....