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This gene is a member of the neuregulin gene family. This gene family encodes ligands for the transmembrane tyrosine kinase receptors ERBB3 and ERBB4 - members of the epidermal growth factor receptor family. Ligand binding activates intracellular signaling cascades and the induction of cellular responses including proliferation, migration, differentiation, and survival or apoptosis. This gene encodes neuregulin 3 (NRG3). NRG3 has been shown to activate the tyrosine phosphorylation of its cognate receptor, ERBB4, and is thought to influence neuroblast proliferation, migration and differentiation by signalling through ERBB4. NRG3 also promotes mammary differentiation during embryogenesis. Linkage studies have implicated this gene as a susceptibility locus for schizophrenia and schizoaffective disorder. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but their biological validity has not been verified.[provided by RefSeq, Sep 2009]
NRG3 (Neuregulin 3) is a Protein Coding gene. Diseases associated with NRG3 include Schizophrenia and Schizoaffective Disorder. Among its related pathways are RET signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and receptor tyrosine kinase binding. An important paralog of this gene is NRG2.
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 |
---|---|---|---|---|---|---|---|---|---|---|
GH10J081874 | Promoter/Enhancer | 1.6 | EPDnew Ensembl ENCODE CraniofacialAtlas | 600.7 | +1.2 | 1211 | 4.8 | KDM1A ZFX SP2 RAD21 CTCF CTBP1 EZH2 ZBTB26 ZNF513 SIN3A | ENSG00000287358 NRG3 piR-38051-045 | |
GH10J082799 | Promoter | 0.3 | EPDnew | 600 | +924.5 | 924545 | 0.1 | NRG3 piR-61945-053 piR-38716-015 | ||
GH10J082816 | Promoter | 0.3 | EPDnew | 600 | +941.6 | 941562 | 0.1 | NRG3 piR-61945-053 HSALNG0079275 | ||
GH10J081847 | Enhancer | 0.5 | Ensembl ENCODE | 12.1 | -27.7 | -27681 | 1 | TEAD4 POU5F1 | NRG3 piR-31470-057 lnc-DYDC1-2 | |
GH10J081846 | Enhancer | 0.3 | Ensembl | 11.6 | -29.4 | -29389 | 0.4 | ATF4 | NRG3 piR-31470-057 lnc-DYDC1-2 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005102 | signaling receptor binding | IEA,IBA | 21873635 |
GO:0008083 | growth factor activity | NAS | 9275162 |
GO:0030297 | transmembrane receptor protein tyrosine kinase activator activity | NAS | 9275162 |
GO:0030971 | receptor tyrosine kinase binding | NAS | 9275162 |
GO:0045499 | chemorepellent activity | IEA,IBA | 21873635 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | NAS | 9275162 |
GO:0005615 | extracellular space | IBA | 21873635 |
GO:0005886 | plasma membrane | IEA | -- |
GO:0005887 | integral component of plasma membrane | NAS | 9275162 |
GO:0016020 | membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Apoptotic Pathways in Synovial Fibroblasts |
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
PPAR Pathway
.66
|
Rac1 Pathway
.65
Glioma Invasiveness
.64
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Rap1 Pathway
.57
Nuclear Receptor Activation by Vitamin-A
.57
|
3 | Signaling by ERBB2 | ||
4 | GAB1 signalosome |
.89
|
|
5 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001558 | regulation of cell growth | NAS | 9275162 |
GO:0007171 | activation of transmembrane receptor protein tyrosine kinase activity | IEA | -- |
GO:0007389 | pattern specification process | IEA | -- |
GO:0007399 | nervous system development | IEA | -- |
GO:0021842 | chemorepulsion involved in interneuron migration from the subpallium to the cortex | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Iloperidone | Approved | Pharma | Antagonist | Dopamine (D2) and serotonin (5HT2) receptor antagonist | 23 |
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Cow (Bos Taurus) |
Mammalia | NRG3 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | NRG3 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Nrg3 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Nrg3 30 |
|
||
Chimpanzee (Pan troglodytes) |
Mammalia | NRG3 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | NRG3 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | NRG3 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | NRG3 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | nrg3 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.31978 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | LOC101882495 30 |
|
||
NRG3 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 10 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
691406 | Uncertain Significance: Hirschsprung disease | 81,878,019(+) | C/G | MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,INTRON_VARIANT | |
691407 | Uncertain Significance: Hirschsprung disease | 82,985,284(+) | A/G | NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT | |
691408 | Uncertain Significance: Hirschsprung disease | 82,985,500(+) | C/T | NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT | |
716399 | Benign: not provided | 81,875,637(+) | C/T | NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT | |
717976 | Benign: not provided | 82,958,962(+) | C/G | MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
schizophrenia |
|
|
schizoaffective disorder |
|
|
hirschsprung disease 1 |
|
|