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FLASH GENE
Symbol NRG3 contributors: mct - updated : 06-09-2016
HGNC name neuregulin 3
HGNC id 7999
Corresponding disease
DEL10Q23 chromosome 10q22q23 deletions and duplications
Location 10q23.1      Physical location : 83.635.069 - 84.746.935
Synonym name
  • neuregulin-3-like polypeptide
  • pro-neuregulin-3, membrane-bound isoform
  • Synonym symbol(s) pro-NRG3, HRG3
    DNA
    TYPE anonymous DNA segment
    STRUCTURE 1111.87 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D10S1786 - D10S134E - NRG3 - D10S551 - D10S532 - qter
    Physical map
    LOC389988 10 similar to nuclear DNA-binding protein; small unique nuclear receptor corepressor; C1D DNA-binding protein LOC389989 10 hypothetical gene supported by BC016284; NM_173177 FLJ13263 10q23.1 hypothetical protein FLJ13263 PLAC9 10q23.2 placenta-specific 9 ANXA11 10q22.3 annexin A11 LOC143243 10q23.1 similar to eukaryotic initiation factor 5A isoform I variant A MAT1A 10q22 methionine adenosyltransferase I, alpha LOC143241 10q23.1 hypothetical protein BC019250 MGC16186 10q23.1 hypothetical protein MGC16186 MGC4248 10q23.1 hypothetical protein MGC4248 DC-TM4F2 10q23.1 tetraspanin similar to TM4SF9 LOC387694 10 similar to hypothetical protein D030001E08 LOC389990 10 similar to Replication protein A 32 kDa subunit (RP-A) (RF-A) (Replication factor-A protein 2) NRG3 10q22-q23 neuregulin 3
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 3689 - 695 brain 1997 9275162
    9 - 3692 - 696 testis 2006 16478787
    11 - 3348 - 499 expressed in the developing human central nervous system 2010 20713722
  • alsos called hFBNRG3
  • human fetal brain NRG3
  • post-translationally regulated isoform of neuregulin 3 with a role in oligodendrocyte survival
  • isoform promoting oligodendrocyte survival via the ERBB4/PI3K/AKT1 pathway, and implicating NRG3-ERBB4 signaling in neurodevelopment and adult brain function
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly Homo sapiens
    Reproductivemale systemtestis  lowly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral  highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductiveepithelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES Hydrophobic
    STRUCTURE
    motifs/domains
  • a N terminal alanine/glycine- rich segment
  • an extracellular EGF-like domain (31 p100 identity with the NRG1 EGF-like domain)
  • two hydrophobic segments functioning as a transmembrane domain
  • a mucin-like S-Triche region wich abundant sites for O-linked glycosylation
  • conjugated GlycoP
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to murine Nrg3
    intraspecies paralog to NRG1
    Homologene
    FAMILY
  • neuregulin family
  • CATEGORY regulatory , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text type I membrane protein and soluble
    basic FUNCTION
  • may be involved in the regulation of trafficking and proteolytic processing
  • increases tyrosine phosphorylation of ERBB4 receptor
  • promotes cell death of prostate cancer cells
  • acting as an oligodendrocyte survival factor by activating the phosphoinositide 3-kinase signaling pathway
  • like NRG1, plays critical roles in the development of the embryonic cerebral cortex via regulation of cortical cell migration and patterning
  • plays pleiotropic roles in neurodevelopment and is a putative susceptibility locus for schizophrenia
  • regulates the distribution of epithelial progenitor cells within the presumptive mammary-forming region during early mammary morphogenesis
  • potential role for NRG3 in brain development and function, which appears to be distinct from its paralog NRG1
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ligand for the ERBB4 receptor tyrosine kinase that plays pleotropic roles in neurodevelopment
  • PTPN21 exerts pro-neuronal survival and neuritic elongation via ERBB4/NRG3 signaling
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL10Q23
    Susceptibility
  • to schizophrenia
  • to developmental delay, cognitive impairment, and autism
  • to Hirschsprung disease
  • Variant & Polymorphism SNP
  • polymorphisms in intron 1 of NRG3 (rs10883866, rs10748842, and rs6584400) increasing the risk of schizophrenia
  • recurrent microdeletions associated with a heterogeneous group of neurodevelopmental disorders, including developmental delay, cognitive impairment, and autism
  • nonsynonymous variant c.1329G>A (p.M443I) and synonymous variants c.828G>A (p.T276T) and c.1365T>A (p.P455P) increase risk of Hirschsprung disease
  • Candidate gene for congenital breast aplasia in del 10q23
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in murine juvenile testes Ra and Fsh induced meiosis indirectly through Sertoli cells when Nrg1 and Nrg3 were upregulated, as Nrg1 amplified itself and Nrg3