NRG3 neuregulin 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NRG3provided by HGNC
Official Full Name: neuregulin 3provided by HGNC
Primary source: HGNC:HGNC:7999
See related: Ensembl:ENSG00000185737 MIM:605533; AllianceGenome:HGNC:7999
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HRG3; pro-NRG3
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 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]
Expression: Biased expression in brain (RPKM 3.4), gall bladder (RPKM 0.5) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 10q23.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (81875194..82987179)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (82749017..83860555)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (83634950..84746935)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Transcytosis and trans-synaptic retention by postsynaptic ErbB4 underlie axonal accumulation of NRG3.
Title: Transcytosis and trans-synaptic retention by postsynaptic ErbB4 underlie axonal accumulation of NRG3.
Association of NRG3 and ERBB4 gene polymorphism with nicotine dependence in Turkish population.
Title: Association of NRG3 and ERBB4 gene polymorphism with nicotine dependence in Turkish population.
Neuregulin 3 rs10748842 polymorphism contributes to the effect of body mass index on cognitive impairment in patients with schizophrenia.
Title: Neuregulin 3 rs10748842 polymorphism contributes to the effect of body mass index on cognitive impairment in patients with schizophrenia.
NRG3 contributes to cognitive deficits in chronic patients with schizophrenia.
Title: NRG3 contributes to cognitive deficits in chronic patients with schizophrenia.
The BRE rs7572644 and NRG3 rs1649942 genetic variants were validated in an independent cohort of EOC Portuguese patients.
Title: Pharmacogenomics in epithelial ovarian cancer first-line treatment outcome: validation of GWAS-associated NRG3 rs1649942 and BRE rs7572644 variants in an independent cohort.
No genetic correlation was found between Hirschsprung disease and the three SNPs at NRG3 (rs10748842, rs10883866 and rs6584400)
Title: Effects of RET, NRG1 and NRG3 Polymorphisms in a Chinese Population with Hirschsprung Disease.
Data show that Williams-Beuren syndrome transcription factor (WSTF) release was mediated by neuregulin-3 (NRG3) following KRASG12V expression in intestinal epithelial cells.
Title: KRASG12 mutant induces the release of the WSTF/NRG3 complex, and contributes to an oncogenic paracrine signaling pathway.
These observations encourage investigation of the neurobiology of NRG3 isoforms and highlight inhibition of NRG3 signaling as a potential target for psychiatric treatment development.
Title: Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders.
common variants of GABRG2, RELN and NRG3 and the GABRG2-RELN-PTCH1 interaction networks might confer altered susceptibility to Hirschsprung disease.
Title: Contribution of Common Variants in GABRG2, RELN and NRG3 and Interaction Networks to the Risk of Hirschsprung Disease.
these data suggest that Nrg3/ErbB4 signaling may be an important factor in nicotine dependence.
Title: Evidence from mouse and man for a role of neuregulin 3 in nicotine dependence.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2011-12-21) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2011-12-21) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Genome-wide association study of retinopathy in individuals without diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits. EBI GWAS Catalog EBI GWAS CatalogPubMed
Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality. EBI GWAS Catalog EBI GWAS CatalogPubMed
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Whole genome association study identifies polymorphisms associated with QT prolongation during iloperidone treatment of schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10S671 (e-PCR)
- UniSTS:6915

SHGC-154958 (e-PCR)
- UniSTS:182281

RH119931 (e-PCR)
- UniSTS:133132

SHGC-30449 (e-PCR)
- UniSTS:1310

G32700 (e-PCR)
- UniSTS:117282

D10S246 (e-PCR)
- UniSTS:18983

NRG3_3103 (e-PCR)
- UniSTS:462376

SHGC-57774 (e-PCR)
- UniSTS:69928

RH121820 (e-PCR)
- UniSTS:134969

D10S1343E (e-PCR)
- UniSTS:151358

D10S228E (e-PCR)
- UniSTS:147525

RH68827 (e-PCR)
- UniSTS:41039

WI-15668 (e-PCR)
- UniSTS:83538

SHGC-82385 (e-PCR)
- UniSTS:104532

SHGC-142257 (e-PCR)
- UniSTS:171350

RH11310 (e-PCR)
- UniSTS:10332

D10S1367E (e-PCR)
- UniSTS:39517

SHGC-35063 (e-PCR)
- UniSTS:72037

RH70340 (e-PCR)
- UniSTS:66930

D10S2242 (e-PCR)
- UniSTS:10878

SHGC-144263 (e-PCR)
- UniSTS:174209

WI-17042 (e-PCR)
- UniSTS:54658

D10S1455 (e-PCR)
- UniSTS:34961

RH80120 (e-PCR)
- UniSTS:87975

D10S1786 (e-PCR), detects polymorphism
- UniSTS:12459

SHGC-105093 (e-PCR)
- UniSTS:169140

D10S2475 (e-PCR)
- UniSTS:71864

RH70354 (e-PCR)
- UniSTS:9662

SHGC-33444 (e-PCR)
- UniSTS:62142

SHGC-36005 (e-PCR)
- UniSTS:69569

NoName (e-PCR)
- UniSTS:484295

A009O11 (e-PCR)
- UniSTS:17867

D10S1620E (e-PCR)
- UniSTS:154059

SHGC-78636 (e-PCR)
- UniSTS:102092

STS-N58117 (e-PCR)
- UniSTS:27087

SHGC-34699 (e-PCR)
- UniSTS:70618

SHGC-57694 (e-PCR)
- UniSTS:39386

RH119289 (e-PCR)
- UniSTS:133851

RH46051 (e-PCR)
- UniSTS:12512

RH120031 (e-PCR)
- UniSTS:133355

RH66478 (e-PCR)
- UniSTS:18156

SHGC-105825 (e-PCR)
- UniSTS:169455

SHGC-33483 (e-PCR)
- UniSTS:83441

RH93468 (e-PCR)
- UniSTS:90874

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables chemorepellent activity	IBA Inferred from Biological aspect of Ancestor more info
enables growth factor activity	NAS Non-traceable Author Statement more info	PubMed
enables receptor ligand activity	IDA Inferred from Direct Assay more info	PubMed
enables receptor tyrosine kinase binding	NAS Non-traceable Author Statement more info	PubMed
enables transmembrane receptor protein tyrosine kinase activator activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in ERBB4 signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in ERBB4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in ERBB4-ERBB4 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in animal organ development	IBA Inferred from Biological aspect of Ancestor more info
involved_in chemorepulsion involved in interneuron migration from the subpallium to the cortex	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in mammary placode formation	IEA Inferred from Electronic Annotation more info
involved_in modulation of chemical synaptic transmission	IDA Inferred from Direct Assay more info	PubMed
involved_in modulation of chemical synaptic transmission	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of neuron migration	IEA Inferred from Electronic Annotation more info
involved_in pattern specification process	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell growth	NAS Non-traceable Author Statement more info	PubMed
involved_in synapse assembly	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: pro-neuregulin-3, membrane-bound isoform

Names: neuregulin-3-like polypeptide

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013373.1 RefSeqGene

Range

4881..1116865

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001010848.4 → NP_001010848.2 pro-neuregulin-3, membrane-bound isoform isoform 1

See identical proteins and their annotated locations for NP_001010848.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

AL096706, AL589782, BC136811, DQ001411

Consensus CDS

CCDS31233.1

UniProtKB/TrEMBL

B4DKH1

Related

ENSP00000361214.2, ENST00000372141.7

Conserved Domains (2) summary

PHA02887
Location:278 → 331

PHA02887; EGF-like protein; Provisional

pfam02158
Location:353 → 486

Neuregulin; Neuregulin family
NM_001165972.1 → NP_001159444.1 pro-neuregulin-3, membrane-bound isoform isoform 2

See identical proteins and their annotated locations for NP_001159444.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a protein (isoform 2) that is one amino acid shorter, compared to isoform 1.

Source sequence(s)

AA704915, AK122886, AL589782, BC136811, DB326565

UniProtKB/TrEMBL

B4DKH1, B9EGV5

Conserved Domains (1) summary

PHA02887
Location:278 → 331

PHA02887; EGF-like protein; Provisional
NM_001165973.2 → NP_001159445.1 pro-neuregulin-3, membrane-bound isoform isoform 3

See identical proteins and their annotated locations for NP_001159445.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) has multiple differences in the presence and absence of exons in the 5' and 3' ends, compared to variant 1. These differences produce a unique 5' UTR and cause translation initiation at a unique start codon, compared to variant 1. The encoded protein (isoform 3; also known as hFBNRG3) has a shorter and distinct N-terminus and 24 additional aa in its C-terminus, compared to isoform 1. Isoform 3 is exclusively expressed in fetal brain and may undergo N-terminal proteolytic processing following its insertion into the plasma membrane.

Source sequence(s)

AA704915, AK122886, AL589782, DB326565, DQ001411, DQ857894

Consensus CDS

CCDS53547.1

UniProtKB/TrEMBL

D9ZHQ5

Related

ENSP00000361215.2, ENST00000372142.6

Conserved Domains (2) summary

PHA02887
Location:38 → 110

PHA02887; EGF-like protein; Provisional

pfam02158
Location:132 → 265

Neuregulin; Neuregulin family
NM_001370081.1 → NP_001357010.1 pro-neuregulin-3, membrane-bound isoform isoform 4

Status: REVIEWED

Source sequence(s)

AL096706, AL136085, AL354749, AL391478, AL513204, AL589782

UniProtKB/TrEMBL

B4DKH1

Conserved Domains (2) summary

PHA02887
Location:278 → 331

PHA02887; EGF-like protein; Provisional

pfam02158
Location:352 → 486

Neuregulin; Neuregulin family
NM_001370082.1 → NP_001357011.1 pro-neuregulin-3, membrane-bound isoform isoform 5

Status: REVIEWED

Source sequence(s)

AC010157, AL096706, AL136085, AL354749, AL391478, AL513204, AL589782

UniProtKB/TrEMBL

D9ZHQ7

Related

ENSP00000451376.1, ENST00000556918.5

Conserved Domains (2) summary

PHA02887
Location:82 → 142

PHA02887; EGF-like protein; Provisional

pfam02158
Location:164 → 297

Neuregulin; Neuregulin family
NM_001370083.1 → NP_001357012.1 pro-neuregulin-3, membrane-bound isoform isoform 6

Status: REVIEWED

Source sequence(s)

AL096706, AL391478
NM_001370084.1 → NP_001357013.1 pro-neuregulin-3, membrane-bound isoform isoform 7

Status: REVIEWED

Description

Transcript Variant: This variant (7) encodes the longest isoform (7).

Source sequence(s)

AL096706, AL136085, AL354749, AL391478, AL513204, AL589782

Consensus CDS

CCDS91287.1

UniProtKB/Swiss-Prot

A4D7U1, P56975, Q0PEH2, Q5VYH3

UniProtKB/TrEMBL

B4DKH1, D9ZHP6

Related

ENSP00000384796.1, ENST00000404547.5

Conserved Domains (2) summary

PHA02887
Location:278 → 331

PHA02887; EGF-like protein; Provisional

pfam02158
Location:353 → 486

Neuregulin; Neuregulin family

RNA

NR_163251.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010157, AL096706, AL136085, AL354749, AL391478, AL513204, AL589782
NR_163252.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL096706, AL136085, AL354749, AL391478, AL513204, AL589782
NR_163253.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL096706, AL096863, AL136085, AL354749, AL391478, AL513204, AL589782

Related

ENST00000602794.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p14 Primary Assembly

Range

81875194..82987179

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017015573.3 → XP_016871062.1 pro-neuregulin-3, membrane-bound isoform isoform X1

UniProtKB/TrEMBL

B4DKH1
XM_017015577.3 → XP_016871066.1 pro-neuregulin-3, membrane-bound isoform isoform X5

UniProtKB/TrEMBL

B4DKH1
XM_017015574.3 → XP_016871063.1 pro-neuregulin-3, membrane-bound isoform isoform X2

UniProtKB/TrEMBL

B4DKH1
XM_017015578.3 → XP_016871067.1 pro-neuregulin-3, membrane-bound isoform isoform X6

UniProtKB/TrEMBL

B4DKH1
XM_017015575.3 → XP_016871064.1 pro-neuregulin-3, membrane-bound isoform isoform X3

UniProtKB/TrEMBL

B4DKH1
XM_017015579.3 → XP_016871068.1 pro-neuregulin-3, membrane-bound isoform isoform X7

UniProtKB/TrEMBL

B4DKH1
XM_017015576.3 → XP_016871065.1 pro-neuregulin-3, membrane-bound isoform isoform X4

UniProtKB/TrEMBL

B4DKH1
XM_017015580.3 → XP_016871069.1 pro-neuregulin-3, membrane-bound isoform isoform X8

UniProtKB/TrEMBL

B4DKH1
XM_011539172.4 → XP_011537474.1 pro-neuregulin-3, membrane-bound isoform isoform X9

UniProtKB/TrEMBL

B4DKH1

Conserved Domains (2) summary

PHA02887
Location:278 → 331

PHA02887; EGF-like protein; Provisional

pfam02158
Location:353 → 487

Neuregulin; Neuregulin family
XM_011539175.4 → XP_011537477.1 pro-neuregulin-3, membrane-bound isoform isoform X12

UniProtKB/TrEMBL

B4DKH1

Conserved Domains (2) summary

PHA02887
Location:278 → 331

PHA02887; EGF-like protein; Provisional

pfam02158
Location:353 → 487

Neuregulin; Neuregulin family
XM_011539173.4 → XP_011537475.1 pro-neuregulin-3, membrane-bound isoform isoform X10

UniProtKB/TrEMBL

B4DKH1

Conserved Domains (1) summary

PHA02887
Location:278 → 331

PHA02887; EGF-like protein; Provisional
XM_047424512.1 → XP_047280468.1 pro-neuregulin-3, membrane-bound isoform isoform X11
XM_017015584.3 → XP_016871073.1 pro-neuregulin-3, membrane-bound isoform isoform X14
XM_017015582.2 → XP_016871071.1 pro-neuregulin-3, membrane-bound isoform isoform X13

UniProtKB/TrEMBL

D9ZHP9

Conserved Domains (2) summary

PHA02887
Location:11 → 71

PHA02887; EGF-like protein; Provisional

pfam02158
Location:93 → 227

Neuregulin; Neuregulin family
XM_024447781.2 → XP_024303549.1 pro-neuregulin-3, membrane-bound isoform isoform X17

UniProtKB/TrEMBL

D9ZHQ8

Related

ENSP00000441201.1, ENST00000545131.5

Conserved Domains (1) summary

pfam02158
Location:3 → 136

Neuregulin; Neuregulin family
XM_011539178.3 → XP_011537480.1 pro-neuregulin-3, membrane-bound isoform isoform X15

UniProtKB/TrEMBL

D9ZHQ8
XM_047424513.1 → XP_047280469.1 pro-neuregulin-3, membrane-bound isoform isoform X16

RNA

XR_001747009.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060934.1 Alternate T2T-CHM13v2.0

Range

82749017..83860555

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054364607.1 → XP_054220582.1 pro-neuregulin-3, membrane-bound isoform isoform X1
XM_054364611.1 → XP_054220586.1 pro-neuregulin-3, membrane-bound isoform isoform X5
XM_054364608.1 → XP_054220583.1 pro-neuregulin-3, membrane-bound isoform isoform X2
XM_054364612.1 → XP_054220587.1 pro-neuregulin-3, membrane-bound isoform isoform X6
XM_054364609.1 → XP_054220584.1 pro-neuregulin-3, membrane-bound isoform isoform X3
XM_054364613.1 → XP_054220588.1 pro-neuregulin-3, membrane-bound isoform isoform X7
XM_054364610.1 → XP_054220585.1 pro-neuregulin-3, membrane-bound isoform isoform X4
XM_054364614.1 → XP_054220589.1 pro-neuregulin-3, membrane-bound isoform isoform X8
XM_054364615.1 → XP_054220590.1 pro-neuregulin-3, membrane-bound isoform isoform X9
XM_054364618.1 → XP_054220593.1 pro-neuregulin-3, membrane-bound isoform isoform X12
XM_054364616.1 → XP_054220591.1 pro-neuregulin-3, membrane-bound isoform isoform X10
XM_054364617.1 → XP_054220592.1 pro-neuregulin-3, membrane-bound isoform isoform X11
XM_054364620.1 → XP_054220595.1 pro-neuregulin-3, membrane-bound isoform isoform X14
XM_054364619.1 → XP_054220594.1 pro-neuregulin-3, membrane-bound isoform isoform X13
XM_054364623.1 → XP_054220598.1 pro-neuregulin-3, membrane-bound isoform isoform X17
XM_054364621.1 → XP_054220596.1 pro-neuregulin-3, membrane-bound isoform isoform X15
XM_054364622.1 → XP_054220597.1 pro-neuregulin-3, membrane-bound isoform isoform X16