NRG2 (neuregulin 2)

Gene

• Entrez ID: 9542
• Gene name: Neuregulin 2
• Gene symbol: NRG2
• Synonyms (NCBI Gene): DON1, HRG2, NTAK
• Chromosome: 5
• Chromosome location: 5q31.2
• Summary: This gene encodes a novel member of the neuregulin family of growth and differentiation factors. Through interaction with the ERBB family of receptors, this protein induces the growth and differentiation of epithelial, neuronal, glial, and other types of

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612709	hsa-miR-8485	HITS-CLIP	23824327
MIRT612708	hsa-miR-4654	HITS-CLIP	23824327
MIRT612707	hsa-miR-4769-5p	HITS-CLIP	23824327
MIRT612706	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT612705	hsa-miR-5089-5p	HITS-CLIP	23824327
MIRT1193915	hsa-miR-1252	CLIP-seq
MIRT1193916	hsa-miR-1253	CLIP-seq
MIRT1193917	hsa-miR-1908	CLIP-seq
MIRT1193918	hsa-miR-3178	CLIP-seq
MIRT1193919	hsa-miR-3184	CLIP-seq
MIRT1193920	hsa-miR-3960	CLIP-seq
MIRT1193921	hsa-miR-423-5p	CLIP-seq
MIRT1193922	hsa-miR-4479	CLIP-seq
MIRT1193923	hsa-miR-4694-5p	CLIP-seq
MIRT1193924	hsa-miR-522	CLIP-seq
MIRT1193925	hsa-miR-658	CLIP-seq
MIRT1193926	hsa-miR-663	CLIP-seq
MIRT1193927	hsa-miR-744	CLIP-seq
MIRT2284813	hsa-miR-766	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005102	Function	Signaling receptor binding	IBA
GO:0005102	Function	Signaling receptor binding	IEA
GO:0005102	Function	Signaling receptor binding	TAS
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007165	Process	Signal transduction	TAS	9168115
GO:0007399	Process	Nervous system development	IEA
GO:0008083	Function	Growth factor activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0035556	Process	Intracellular signal transduction	IBA
GO:0038130	Process	ERBB4 signaling pathway	IBA
GO:0048513	Process	Animal organ development	IBA

Other IDs

• MIM: 603818
• HGNC: 7998
• e!Ensembl: ENSG00000158458

Protein

• UniProt ID: O14511
• Protein name: Pro-neuregulin-2, membrane-bound isoform (Pro-NRG2) [Cleaved into: Neuregulin-2 (NRG-2) (Divergent of neuregulin-1) (DON-1) (Neural- and thymus-derived activator for ERBB kinases) (NTAK)]
• Protein function: Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. May also promote the heterodimerizatio
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07679	I-set	238 → 328	Immunoglobulin I-set domain	Domain
  PF02158	Neuregulin	430 → 831	Neuregulin intracellular region	Disordered

• Tissue specificity: TISSUE SPECIFICITY: Restricted to the cerebellum in the adult.
• Sequence:

  MRQVCCSALPPPPLEKGRCSSYSDSSSSSSERSSSSSSSSSESGSSSRSSSNNSSISRPA
  APPEPRPQQQPQPRSPAARRAAARSRAAAAGGMRRDPAPGFSMLLFGVSLACYSPSLKSV
  QDQAYKAPVVVEGKVQGLVPAGGSSSNSTREPPASGRVALVKVLDKWPLRSGGLQREQVI
  SVGSCVPLERNQRYIFFLEPTEQPLVFKTAFAPLDTNGKNLKKEVGKILCTDCATRPKLK
  KMKSQTGQVGEKQSLKCEAAAGNPQPSYRWFKDGKELNRSRDIRIKYGNGRKNSRLQFNK
  VKVEDAGEYVCEAENILGKDTVRGRLYVNSVSTTLSSWSGHARKCNETAKSYCVNGGVCY
  YIEGINQLSCKCPNGFFGQRCLEKLPLRLYMPDPKQKAEELYQKRVLTITGICVALLVVG
  IVCVVAYCKTKKQRKQMHNHLRQNMCPAHQNRSLANGPSHPRLDPEEIQMADYISKNVPA
  TDHVIRRETETTFSGSHSCSPSHHCSTATPTSSHRHESHTWSLERSESLTSDSQSGIMLS
  SVGTSKCNSPACVEARARRAAAYNLEERRRATAPPYHDSVDSLRDSPHSERYVSALTTPA
  RLSPVDFHYSLATQVPTFEITSPNSAHAVSLPPAAPISYRLAEQQPLLRHPAPPGPGPGP
  GPGPGPGADMQRSYDSYYYPAAGPGPRRGTCALGGSLGSLPASPFRIPEDDEYETTQECA
  PPPPPRPRARGASRRTSAGPRRWRRSRLNGLAAQRARAARDSLSLSSGSGGGSASASDDD
  ADDADGALAAESTPFLGLRGAHDALRSDSPPLCPAADSRTYYSLDSHSTRASSRHSRGPP
  PRAKQDSAPL

• Sequence length: 850

Pathways

KEGG:

EGFR tyrosine kinase inhibitor resistance
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
GRB7 events in ERBB2 signaling
Downregulation of ERBB2:ERBB3 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
ASTROCYTOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autism spectrum disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DISABILITY	—	Disgenet, GenCC Disgenet, GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Breast Neoplasms	Breast neoplasm	Pubtator	17962208, 23912956, 33176622	Associate	★☆☆☆☆ Found in Text Mining only
Charcot-Marie-Tooth Disease	Charcot-Marie-Tooth Disease	BEFREE	10369162		★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	BEFREE	17563728		★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	Pubtator	17563728	Associate	★☆☆☆☆ Found in Text Mining only
Glaucoma 1 Open Angle A	Glaucoma	Pubtator	17563728	Associate	★☆☆☆☆ Found in Text Mining only
Glaucoma, Open-Angle	Glaucoma	LHGDN	17563728		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	34054873	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	34054873, 34284546	Associate	★☆☆☆☆ Found in Text Mining only
Huntington Disease	Huntington disease	Pubtator	33049985	Associate	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung Neoplasms	BEFREE	28722770		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	17962208		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	30637711		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	30123134		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	17962208		★☆☆☆☆ Found in Text Mining only
Mental disorders	Mental Disorders	BEFREE	28322273, 31838721		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	35677537	Associate	★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	30637711		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	32264916	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	28322273		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Stomach Carcinoma	Stomach Carcinoma	BEFREE	30123134		★☆☆☆☆ Found in Text Mining only