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FLASH GENE

Symbol

NRG3

contributors: mct - updated : 06-09-2016

HGNC name	neuregulin 3
HGNC id	7999

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001165972 9 - 3689 NP_001159444 - 695 brain 1997 9275162 NM_001010848 9 - 3692 NP_001010848 - 696 testis 2006 16478787 NM_001165973 11 - 3348 NP_001159445 - 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)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain       highly Homo sapiens Reproductive male system testis     lowly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central     highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Reproductive epithelial 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