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NRG3 neuregulin 3 [ Homo sapiens (human) ]

Gene ID: 10718, updated on 3-Apr-2024

Summary

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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

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Location:
10q23.1
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (81875194..82987179)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (82749017..83860555)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (83634950..84746935)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105378390 Neighboring gene uncharacterized LOC124902549 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:83635899-83636661 Neighboring gene NANOG hESC enhancer GRCh37_chr10:83641632-83642192 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr10:83703221-83703801 Neighboring gene MPRA-validated peak1034 silencer Neighboring gene uncharacterized LOC124902472 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr10:84047967-84049166 Neighboring gene NRG3 antisense RNA 1 Neighboring gene RNA, U6 small nuclear 441, pseudogene Neighboring gene NANOG hESC enhancer GRCh37_chr10:84156597-84157098 Neighboring gene NANOG hESC enhancer GRCh37_chr10:84435047-84435611 Neighboring gene Sharpr-MPRA regulatory region 14045 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:84502591-84502759 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr10:84518678-84519389 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:84570168-84570356 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr10:84715398-84716597 Neighboring gene NANOG hESC enhancer GRCh37_chr10:84720206-84720727 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr10:84721457-84722098 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr10:84838063-84838624 Neighboring gene RNA, U6 small nuclear 478, pseudogene Neighboring gene uncharacterized LOC107984187

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: 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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Related articles in PubMed

  1. Neuregulin 3 rs10748842 polymorphism contributes to the effect of body mass index on cognitive impairment in patients with schizophrenia. Zhou Y, et al. Transl Psychiatry, 2020 Feb 11. PMID 32066712, Free PMC Article
  2. NRG3 contributes to cognitive deficits in chronic patients with schizophrenia. Li Z, et al. Schizophr Res, 2020 Jan. PMID 31753594
  3. Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders. Paterson C, et al. Am J Psychiatry, 2017 Mar 1. PMID 27771971, Free PMC Article
  4. Effects of neuregulin 3 genotype on human prefrontal cortex physiology. Tost H, et al. J Neurosci, 2014 Jan 15. PMID 24431462, Free PMC Article
  5. NRG3 gene is associated with the risk and age at onset of Alzheimer disease. Wang KS, et al. J Neural Transm (Vienna), 2014 Feb. PMID 24061483

See all (52) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. NRG3 contributes to cognitive deficits in chronic patients with schizophrenia.
    Title: NRG3 contributes to cognitive deficits in chronic patients with schizophrenia.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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
Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits.
EBI GWAS Catalog
Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.
EBI GWAS Catalog
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
EBI GWAS Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
EBI GWAS Catalog
Whole genome association study identifies polymorphisms associated with QT prolongation during iloperidone treatment of schizophrenia.
EBI GWAS Catalog

Variation

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See Variation Viewer (GRCh37.p13)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

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 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

  1. NG_013373.1 RefSeqGene

    Range
    4881..1116865
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

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

    Status: REVIEWED

    Source sequence(s)
    AL096706, AL391478

  7. 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

  1. NR_163251.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC010157, AL096706, AL136085, AL354749, AL391478, AL513204, AL589782

  2. NR_163252.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL096706, AL136085, AL354749, AL391478, AL513204, AL589782

  3. 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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    81875194..82987179
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    UniProtKB/TrEMBL
    B4DKH1

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

    UniProtKB/TrEMBL
    B4DKH1

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

    UniProtKB/TrEMBL
    B4DKH1

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

    UniProtKB/TrEMBL
    B4DKH1

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

    UniProtKB/TrEMBL
    B4DKH1

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

    UniProtKB/TrEMBL
    B4DKH1

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

    UniProtKB/TrEMBL
    B4DKH1

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

    UniProtKB/TrEMBL
    B4DKH1

  9. 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

  10. 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

  11. 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

  12. XM_047424512.1 → XP_047280468.1  pro-neuregulin-3, membrane-bound isoform isoform X11

  13. XM_017015584.3 → XP_016871073.1  pro-neuregulin-3, membrane-bound isoform isoform X14

  14. 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

  15. 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

  16. XM_011539178.3 → XP_011537480.1  pro-neuregulin-3, membrane-bound isoform isoform X15

    UniProtKB/TrEMBL
    D9ZHQ8

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

RNA

  1. XR_001747009.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    82749017..83860555
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054364607.1 → XP_054220582.1  pro-neuregulin-3, membrane-bound isoform isoform X1

  2. XM_054364611.1 → XP_054220586.1  pro-neuregulin-3, membrane-bound isoform isoform X5

  3. XM_054364608.1 → XP_054220583.1  pro-neuregulin-3, membrane-bound isoform isoform X2

  4. XM_054364612.1 → XP_054220587.1  pro-neuregulin-3, membrane-bound isoform isoform X6

  5. XM_054364609.1 → XP_054220584.1  pro-neuregulin-3, membrane-bound isoform isoform X3

  6. XM_054364613.1 → XP_054220588.1  pro-neuregulin-3, membrane-bound isoform isoform X7

  7. XM_054364610.1 → XP_054220585.1  pro-neuregulin-3, membrane-bound isoform isoform X4

  8. XM_054364614.1 → XP_054220589.1  pro-neuregulin-3, membrane-bound isoform isoform X8

  9. XM_054364615.1 → XP_054220590.1  pro-neuregulin-3, membrane-bound isoform isoform X9

  10. XM_054364618.1 → XP_054220593.1  pro-neuregulin-3, membrane-bound isoform isoform X12

  11. XM_054364616.1 → XP_054220591.1  pro-neuregulin-3, membrane-bound isoform isoform X10

  12. XM_054364617.1 → XP_054220592.1  pro-neuregulin-3, membrane-bound isoform isoform X11

  13. XM_054364620.1 → XP_054220595.1  pro-neuregulin-3, membrane-bound isoform isoform X14

  14. XM_054364619.1 → XP_054220594.1  pro-neuregulin-3, membrane-bound isoform isoform X13

  15. XM_054364623.1 → XP_054220598.1  pro-neuregulin-3, membrane-bound isoform isoform X17

  16. XM_054364621.1 → XP_054220596.1  pro-neuregulin-3, membrane-bound isoform isoform X15

  17. XM_054364622.1 → XP_054220597.1  pro-neuregulin-3, membrane-bound isoform isoform X16

RNA

  1. XR_008488156.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P56975.1 GenPept UniProtKB/Swiss-Prot:P56975

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