NRG3 (neuregulin 3)

Gene

• Entrez ID: 10718
• Gene name: Neuregulin 3
• Gene symbol: NRG3
• Synonyms (NCBI Gene): HRG3, pro-NRG3
• Chromosome: 10
• Chromosome location: 10q23.1
• Summary: 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 signalin

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs138878772	G>A	Benign, likely-pathogenic	Genic downstream transcript variant, missense variant, non coding transcript variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1193928	hsa-miR-1267	CLIP-seq
MIRT1193929	hsa-miR-1470	CLIP-seq
MIRT1193930	hsa-miR-188-5p	CLIP-seq
MIRT1193931	hsa-miR-3074-5p	CLIP-seq
MIRT1193932	hsa-miR-3124-3p	CLIP-seq
MIRT1193933	hsa-miR-3140-5p	CLIP-seq
MIRT1193934	hsa-miR-3183	CLIP-seq
MIRT1193935	hsa-miR-330-3p	CLIP-seq
MIRT1193936	hsa-miR-3591-5p	CLIP-seq
MIRT1193937	hsa-miR-3606	CLIP-seq
MIRT1193938	hsa-miR-3653	CLIP-seq
MIRT1193939	hsa-miR-3658	CLIP-seq
MIRT1193940	hsa-miR-4422	CLIP-seq
MIRT1193941	hsa-miR-4462	CLIP-seq
MIRT1193942	hsa-miR-4511	CLIP-seq
MIRT1193943	hsa-miR-4539	CLIP-seq
MIRT1193944	hsa-miR-4637	CLIP-seq
MIRT1193945	hsa-miR-4667-3p	CLIP-seq
MIRT1193946	hsa-miR-4723-3p	CLIP-seq
MIRT1193947	hsa-miR-4724-5p	CLIP-seq
MIRT1193948	hsa-miR-4753-3p	CLIP-seq
MIRT1193949	hsa-miR-548b-3p	CLIP-seq
MIRT1193950	hsa-miR-921	CLIP-seq
MIRT1193928	hsa-miR-1267	CLIP-seq
MIRT1193931	hsa-miR-3074-5p	CLIP-seq
MIRT2056235	hsa-miR-3121-3p	CLIP-seq
MIRT1193932	hsa-miR-3124-3p	CLIP-seq
MIRT1193934	hsa-miR-3183	CLIP-seq
MIRT1193935	hsa-miR-330-3p	CLIP-seq
MIRT2056236	hsa-miR-3671	CLIP-seq
MIRT1193940	hsa-miR-4422	CLIP-seq
MIRT2056237	hsa-miR-4427	CLIP-seq
MIRT2056238	hsa-miR-4643	CLIP-seq
MIRT1193946	hsa-miR-4723-3p	CLIP-seq
MIRT1193948	hsa-miR-4753-3p	CLIP-seq
MIRT1193928	hsa-miR-1267	CLIP-seq
MIRT1193931	hsa-miR-3074-5p	CLIP-seq
MIRT1193932	hsa-miR-3124-3p	CLIP-seq
MIRT1193934	hsa-miR-3183	CLIP-seq
MIRT1193935	hsa-miR-330-3p	CLIP-seq
MIRT1193940	hsa-miR-4422	CLIP-seq
MIRT1193946	hsa-miR-4723-3p	CLIP-seq
MIRT1193948	hsa-miR-4753-3p	CLIP-seq
MIRT2391744	hsa-miR-4433	CLIP-seq
MIRT2391745	hsa-miR-4459	CLIP-seq
MIRT2391746	hsa-miR-4762-5p	CLIP-seq
MIRT2391747	hsa-miR-4768-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001558	Process	Regulation of cell growth	NAS	9275162
GO:0005102	Function	Signaling receptor binding	IEA
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	NAS	9275162
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	12466964
GO:0005615	Component	Extracellular space	IEA
GO:0005615	Component	Extracellular space	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	NAS	9275162
GO:0007389	Process	Pattern specification process	IEA
GO:0007399	Process	Nervous system development	IEA
GO:0007416	Process	Synapse assembly	IEA
GO:0008083	Function	Growth factor activity	IEA
GO:0008083	Function	Growth factor activity	NAS	9275162
GO:0016020	Component	Membrane	IEA
GO:0021842	Process	Chemorepulsion involved in interneuron migration from the subpallium to the cortex	IEA
GO:0030297	Function	Transmembrane receptor protein tyrosine kinase activator activity	NAS	9275162
GO:0030879	Process	Mammary gland development	IEA
GO:0030971	Function	Receptor tyrosine kinase binding	NAS	9275162
GO:0035556	Process	Intracellular signal transduction	IBA
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0038130	Process	ERBB4 signaling pathway	IBA
GO:0038130	Process	ERBB4 signaling pathway	IDA	12466964
GO:0038130	Process	ERBB4 signaling pathway	IEA
GO:0038138	Process	ERBB4-ERBB4 signaling pathway	IEA
GO:0045202	Component	Synapse	IEA
GO:0045499	Function	Chemorepellent activity	IBA
GO:0045499	Function	Chemorepellent activity	IEA
GO:0048018	Function	Receptor ligand activity	IDA	12466964
GO:0048018	Function	Receptor ligand activity	IEA
GO:0048513	Process	Animal organ development	IBA
GO:0050804	Process	Modulation of chemical synaptic transmission	IDA	29114105
GO:0050804	Process	Modulation of chemical synaptic transmission	IMP	29114105
GO:0060596	Process	Mammary placode formation	IEA
GO:0098978	Component	Glutamatergic synapse	IDA	29114105
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0098978	Component	Glutamatergic synapse	IMP	29114105
GO:2001223	Process	Negative regulation of neuron migration	IEA

Other IDs

• MIM: 605533
• HGNC: 7999
• e!Ensembl: ENSG00000185737

Protein

• UniProt ID: P56975
• Protein name: Pro-neuregulin-3, membrane-bound isoform (Pro-NRG3) [Cleaved into: Neuregulin-3 (NRG-3)]
• Protein function: Direct ligand for the ERBB4 tyrosine kinase receptor. Binding results in ligand-stimulated tyrosine phosphorylation and activation of the receptor. Does not bind to the EGF receptor, ERBB2 or ERBB3 receptors. May be a survival factor for oligode
• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in most regions of the brain with the exception of corpus callosum. Expressed at lower level in testis. Not detected in heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, ovary,
• Sequence:

  MSEGAAAASPPGAASAAAASAEEGTAAAAAAAAAGGGPDGGGEGAAEPPRELRCSDCIVW
  NRQQTWLCVVPLFIGFIGLGLSLMLLKWIVVGSVKEYVPTDLVDSKGMGQDPFFLSKPSS
  FPKAMETTTTTTSTTSPATPSAGGAASSRTPNRISTRLTTITRAPTRFPGHRVPIRASPR
  STTARNTAAPATVPSTTAPFFSSSTLGSRPPVPGTPSTQAMPSWPTAAYATSSYLHDSTP
  SWTLSPFQDAASSSSSSSSSATTTTPETSTSPKFHTTTYSTERSEHFKPCRDKDLAYCLN
  DGECFVIETLTGSHKHCRCKEGYQGVRCDQFLPKTDSILSDPTDHLGIEFMESEEVYQRQ
  VLSISCIIFGIVIVGMFCAAFYFKSKKQAKQIQEQLKVPQNGKSYSLKASSTMAKSENLV
  KSHVQLQNYSKVERHPVTALEKMMESSFVGPQSFPEVPSPDRGSQSVKHHRSLSSCCSPG
  QRSGMLHRNAFRRTPPSPRSRLGGIVGPAYQQLEESRIPDQDTIPCQGIEVRKTISHLPI
  QLWCVERPLDLKYSSSGLKTQRNTSINMQLPSRETNPYFNSLEQKDLVGYSSTRASSVPI
  IPSVGLEETCLQMPGISEVKSIKWCKNSYSADVVNVSIPVSDCLIAEQQEVKILLETVQE
  QIRILTDARRSEDYELASVETEDSASENTAFLPLSPTAKSEREAQFVLRNEIQRDSALTK
  

• Sequence length: 720

Pathways

KEGG:

ErbB signaling pathway
Amyotrophic lateral sclerosis

Reactome:

Signaling by ERBB2
Signaling by ERBB4
SHC1 events in ERBB2 signaling
PI3K events in ERBB4 signaling
SHC1 events in ERBB4 signaling
PIP3 activates AKT signaling
GRB2 events in ERBB2 signaling
PI3K events in ERBB2 signaling
Constitutive Signaling by Aberrant PI3K in Cancer
RAF/MAP kinase cascade
ERBB2 Regulates Cell Motility
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
ERBB2 Activates PTK6 Signaling
Downregulation of ERBB2 signaling
Signaling by ERBB2 KD Mutants
Signaling by ERBB2 TMD/JMD mutants

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Aganglionic megacolon	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	Disgenet, GWAS catalog Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CAROTID ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC KIDNEY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOR VISION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC NEPHROPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EATING DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ENDOMETRIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HIRSCHSPRUNG DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTERSTITIAL LUNG DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTIPLE MYELOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINOPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SUBSTANCE ABUSE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYSTEMIC LUPUS ERYTHEMATOSUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENOUS THROMBOEMBOLISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	40631452	Associate	★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	23999525		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	23999525		★☆☆☆☆ Found in Text Mining only
Astrocytoma	Astrocytoma	Pubtator	37932833	Associate	★☆☆☆☆ Found in Text Mining only
Attention Deficit Disorder	Attention Deficit Hyperactivity Disorder	BEFREE	22831755		★☆☆☆☆ Found in Text Mining only
Attention Deficit Disorder with Hyperactivity	Attention deficit hyperactivity disorder	Pubtator	22831755	Associate	★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	BEFREE	22831755		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autism Spectrum Disorder	Autism	Pubtator	22952857	Associate	★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	20713722	Associate	★☆☆☆☆ Found in Text Mining only
Autosomal dominant compelling helio ophthalmic outburst syndrome	Achoo syndrome	GWASCAT_DG	27182965		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	PSYGENET_DG	19765633, 22831755		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar Disorder	BEFREE	22831755, 27771971		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar disorder	Pubtator	22831755, 27063557, 27771971	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar I disorder	Bipolar Disorder	BEFREE	19765633		★☆☆☆☆ Found in Text Mining only
Bone Marrow Diseases	Bone marrow diseases	Pubtator	20465808	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	27771971	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	18418701, 9772300		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	30287910		★☆☆☆☆ Found in Text Mining only
Chronic schizophrenia	Schizophrenia	BEFREE	31753594		★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognition disorder	Pubtator	20713722, 22831755, 32066712	Associate	★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognitive disorder	BEFREE	22831755, 31753594		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	33078631	Associate	★☆☆☆☆ Found in Text Mining only
Delusions	Delusions	BEFREE	20548296, 20713722, 21762460		★☆☆☆☆ Found in Text Mining only
Depressive Disorder Major	Major depressive disorder	Pubtator	27771971	Associate	★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	20713722	Associate	★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	33577492	Associate	★☆☆☆☆ Found in Text Mining only
Epithelial ovarian cancer	Ovarian cancer	BEFREE	30287910		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Neoplasms	Gastrointestinal neoplasm	Pubtator	34484469	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	34054873	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	34054873	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	20713722		★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	20465808	Associate	★☆☆☆☆ Found in Text Mining only
Hirschsprung Disease	Hirschsprung Disease	BEFREE	22589734, 23315268, 27889765, 28256518		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hirschsprung Disease	Hirschsprung disease	Pubtator	22589734, 27889765, 28256518	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Impaired cognition	Impaired Cognition	BEFREE	22831755, 24061483, 31753594		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	GWASCAT_DG	27903959		★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	BEFREE	27771971		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	18418701, 9772300		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	17962208		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	24709886	Associate	★☆☆☆☆ Found in Text Mining only
Mood Disorders	Mood Disorder	BEFREE	27771971		★☆☆☆☆ Found in Text Mining only
Mood Disorders	Mood disorder	Pubtator	27771971	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	20465808, 25268740	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Multiple Myeloma	Multiple myeloma	BEFREE	25268740		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myocardial Infarction	Myocardial Infarction	BEFREE	18521091		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	27771971		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	20713722, 30356120		★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychotic disorders	Pubtator	22831755	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	18708184, 19118813, 19765633, 20548296, 20713722, 21762460, 22831755, 22981155, 24431462, 27771971, 28556469, 30328115, 31753594		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	Pubtator	19118813, 20713722, 21762460, 22831755, 22952857, 27771971, 31596458, 32066712	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	CTD_human_DG	20713722		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	Pubtator	27771971	Stimulate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Unipolar Depression	Mental Depression	BEFREE	27771971		★☆☆☆☆ Found in Text Mining only