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RTN4 reticulon 4 [ Homo sapiens (human) ]

Gene ID: 57142, updated on 7-Apr-2024

Summary

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Official Symbol
RTN4provided by HGNC
Official Full Name
reticulon 4provided by HGNC
Primary source
HGNC:HGNC:14085
See related
Ensembl:ENSG00000115310 MIM:604475; AllianceGenome:HGNC:14085
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
ASY; NSP; NOGO; RTN-X; NSP-CL; RTN4-A; RTN4-C; RTN4-B1; RTN4-B2; NI220/250; Nbla00271; Nbla10545
Summary
This gene belongs to the family of reticulon encoding genes. Reticulons are associated with the endoplasmic reticulum, and are involved in neuroendocrine secretion or in membrane trafficking in neuroendocrine cells. The product of this gene is a potent neurite outgrowth inhibitor which may also help block the regeneration of the central nervous system in higher vertebrates. Alternatively spliced transcript variants derived both from differential splicing and differential promoter usage and encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in fat (RPKM 122.1), brain (RPKM 104.7) and 24 other tissues See more
Orthologs
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Genomic context

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Location:
2p16.1
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (54972189..55137831, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (54969379..55135031, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (55199325..55364967, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15770 Neighboring gene EML6 antisense RNA 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:55005745-55005892 Neighboring gene EMAP like 6 Neighboring gene RNA, U7 small nuclear 81 pseudogene Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:55130773-55131972 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:55177255-55178454 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:55194629-55195622 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:55201598-55201799 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15771 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11493 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15772 Neighboring gene RNA, U6 small nuclear 433, pseudogene Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:55276593-55277405 Neighboring gene uncharacterized LOC105374662 Neighboring gene Sharpr-MPRA regulatory region 4359 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:55360796-55361708 Neighboring gene CRISPRi-validated cis-regulatory element chr2.2087 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15775 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15776 Neighboring gene clathrin heavy chain linker domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11496 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15777 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15778 Neighboring gene CDPF1 pseudogene 1 Neighboring gene ribosomal protein S27a

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. Association of RTN4 indel polymorphisms with the risk of tumorigenesis in the Chinese Han population. Ou X, et al. Cell Mol Biol (Noisy-le-grand), 2023 Feb 28. PMID 37224043
  2. Association of Nogo-A Gene Polymorphisms with Cerebral Palsy in Southern China: A Case-Control Study. Wang Y, et al. Dev Neurosci, 2023. PMID 36323241, Free PMC Article
  3. Dynamic induction of the myelin-associated growth inhibitor Nogo-A in perilesional plasticity regions after human spinal cord injury. Schwaiger C, et al. Brain Pathol, 2023 Jan. PMID 35698271, Free PMC Article
  4. Nogo-B promotes invasion and metastasis of nasopharyngeal carcinoma via RhoA-SRF-MRTFA pathway. Wang J, et al. Cell Death Dis, 2022 Jan 24. PMID 35075114, Free PMC Article
  5. Inhibition of high-fat diet-induced obesity via reduction of ER-resident protein Nogo occurs through multiple mechanisms. Wang X, et al. J Biol Chem, 2022 Feb. PMID 34998825, Free PMC Article

See all (274) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. RTN3 and RTN4: Architects of SARS-CoV-2 replication organelles.
    Title: RTN3 and RTN4: Architects of SARS-CoV-2 replication organelles.
  2. Association of RTN4 indel polymorphisms with the risk of tumorigenesis in the Chinese Han population.
    Title: Association of RTN4 indel polymorphisms with the risk of tumorigenesis in the Chinese Han population.
  3. Nogo-A and LINGO-1: Two Important Targets for Remyelination and Regeneration.
    Title: Nogo-A and LINGO-1: Two Important Targets for Remyelination and Regeneration.
  4. Association of Nogo-A Gene Polymorphisms with Cerebral Palsy in Southern China: A Case-Control Study.
    Title: Association of Nogo-A Gene Polymorphisms with Cerebral Palsy in Southern China: A Case-Control Study.
  5. Dynamic induction of the myelin-associated growth inhibitor Nogo-A in perilesional plasticity regions after human spinal cord injury.
    Title: Dynamic induction of the myelin-associated growth inhibitor Nogo-A in perilesional plasticity regions after human spinal cord injury.
  6. An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age.
    Title: An Rtn4/Nogo-A-interacting micropeptide modulates synaptic plasticity with age.
  7. Inhibition of high-fat diet-induced obesity via reduction of ER-resident protein Nogo occurs through multiple mechanisms.
    Title: Inhibition of high-fat diet-induced obesity via reduction of ER-resident protein Nogo occurs through multiple mechanisms.
  8. Nogo-B promotes invasion and metastasis of nasopharyngeal carcinoma via RhoA-SRF-MRTFA pathway.
    Title: Nogo-B promotes invasion and metastasis of nasopharyngeal carcinoma via RhoA-SRF-MRTFA pathway.
  9. CircRTN4 promotes pancreatic cancer progression through a novel CircRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein.
    Title: CircRTN4 promotes pancreatic cancer progression through a novel CircRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein.
  10. Co-Expression of Nogo-A in Dopaminergic Neurons of the Human Substantia Nigra Pars Compacta Is Reduced in Parkinson's Disease.
    Title: Co-Expression of Nogo-A in Dopaminergic Neurons of the Human Substantia Nigra Pars Compacta Is Reduced in Parkinson's Disease.
Submit: New GeneRIF Correction See all GeneRIFs (120)

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

EBI GWAS Catalog

Description
Common body mass index-associated variants confer risk of extreme obesity.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of reticulon 4 (RTN4) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed
Vpu vpu HIV-1 Vpu is identified to have a physical interaction with reticulon 4 (RTN4) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

Go to the HIV-1, Human Interaction Database

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

Potential readthrough

Included gene: CLHC1

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding HDA PubMed 
enables cadherin binding HDA PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in apoptotic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in axonal fasciculation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in blastocyst formation IEA
Inferred from Electronic Annotation
more info
  
involved_in brain development IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cardiac epithelial to mesenchymal transition IEA
Inferred from Electronic Annotation
more info
  
involved_in cerebral cortex radial glia-guided migration ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in endoplasmic reticulum tubular network formation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in endoplasmic reticulum tubular network formation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in endoplasmic reticulum tubular network membrane organization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in endoplasmic reticulum tubular network organization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in intracellular sphingolipid homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in modulation of chemical synaptic transmission IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of amyloid-beta formation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of axon extension IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of cell growth IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in neuron differentiation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in nuclear pore complex assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of ERBB3 signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of epithelial cell migration IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of mammary gland epithelial cell proliferation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of protein localization to endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of toll-like receptor 9 signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein localization to lysosome ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein stabilization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of apoptotic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in regulation of branching morphogenesis of a nerve ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
located_in anchoring junction IEA
Inferred from Electronic Annotation
more info
  
located_in endoplasmic reticulum HDA PubMed 
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
  
located_in endoplasmic reticulum NAS
Non-traceable Author Statement
more info
 PubMed 
is_active_in endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum tubular network IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum tubular network membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
is_active_in neuron projection IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nuclear envelope IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
is_active_in postsynaptic density IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in synapse ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
reticulon-4
Names
Human NogoA
My043 protein
foocen
neurite growth inhibitor 220
neurite outgrowth inhibitor
neuroendocrine-specific protein C homolog
reticulon 5

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_029037.2 RefSeqGene

    Range
    92381..170643
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001321859.2 → NP_001308788.1  reticulon-4 isoform E

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6), along with variants 5, 7, 8, 9, 10, and 11, encodes isoform E.
    Source sequence(s)
    AC093165, AY123245, BC150182
    Consensus CDS
    CCDS1852.1
    UniProtKB/TrEMBL
    Q53RF4
    Related
    ENSP00000385650.1, ENST00000404909.5
    Conserved Domains (1) summary
    pfam02453
    Location:799 → 963
    Reticulon; Reticulon

  2. NM_001321860.1 → NP_001308789.1  reticulon-4 isoform E

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7), along with variants 5, 6, 8, 9, 10, and 11, encodes isoform E.
    Source sequence(s)
    AY123246, BC150182
    Consensus CDS
    CCDS1852.1
    UniProtKB/TrEMBL
    Q53RF4
    Related
    ENSP00000378109.2, ENST00000394611.6
    Conserved Domains (1) summary
    pfam02453
    Location:799 → 963
    Reticulon; Reticulon

  3. NM_001321861.2 → NP_001308790.1  reticulon-4 isoform E

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8), along with variants 5, 6, 7, 9, 10, and 11, encodes isoform E.
    Source sequence(s)
    AY123247, BC150182
    Consensus CDS
    CCDS1852.1
    UniProtKB/TrEMBL
    Q53RF4
    Conserved Domains (1) summary
    pfam02453
    Location:799 → 963
    Reticulon; Reticulon

  4. NM_001321862.2 → NP_001308791.1  reticulon-4 isoform E

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9), along with variants 5, 6, 7, 8, and 10, encodes isoform E.
    Source sequence(s)
    AY123249, BC150182, DB094021
    Consensus CDS
    CCDS1852.1
    UniProtKB/TrEMBL
    Q53RF4
    Conserved Domains (1) summary
    pfam02453
    Location:799 → 963
    Reticulon; Reticulon

  5. NM_001321863.2 → NP_001308792.1  reticulon-4 isoform E

    Status: REVIEWED

    Description
    Transcript Variant: This variant (10), along with variants 5, 6, 7, 8, 9, and 11, encodes isoform E.
    Source sequence(s)
    AC093165, AY123250, BC150182
    Consensus CDS
    CCDS1852.1
    UniProtKB/TrEMBL
    Q53RF4
    Related
    ENSP00000384471.1, ENST00000405240.5
    Conserved Domains (1) summary
    pfam02453
    Location:799 → 963
    Reticulon; Reticulon

  6. NM_001321904.2 → NP_001308833.1  reticulon-4 isoform E

    Status: REVIEWED

    Description
    Transcript Variant: This variant (11), along with variants 5, 6, 7, 8, 9, and 10, encodes isoform E.
    Source sequence(s)
    AC013414, AC092461, AC093165, BC150182
    Consensus CDS
    CCDS1852.1
    UniProtKB/TrEMBL
    Q53RF4
    Conserved Domains (1) summary
    pfam02453
    Location:799 → 963
    Reticulon; Reticulon

  7. NM_007008.3 → NP_008939.1  reticulon-4 isoform C

    See identical proteins and their annotated locations for NP_008939.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), also known as Foocen-S and Nogo-C, differs in the 5' UTR and the 5' coding region, compared to variant 1. The resulting isoform (C) contains a distinct N-terminus, compared to isoform A.
    Source sequence(s)
    AF125103, AF132048, AI671568, AY102276
    Consensus CDS
    CCDS42685.1
    UniProtKB/TrEMBL
    A6XGP7
    Related
    ENSP00000378107.2, ENST00000394609.6
    Conserved Domains (1) summary
    pfam02453
    Location:12 → 176
    Reticulon

  8. NM_020532.5 → NP_065393.1  reticulon-4 isoform A

    See identical proteins and their annotated locations for NP_065393.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1), also known as Nogo-A and RTN-XL, represents the longest transcript, and encodes the longest isoform (A).
    Source sequence(s)
    AF125103, AF132048, AY123250, BC016165
    Consensus CDS
    CCDS42684.1
    UniProtKB/Swiss-Prot
    O94962, Q7L7Q5, Q7L7Q6, Q7L7Q8, Q8IUA4, Q96B16, Q9BXG5, Q9H212, Q9H3I3, Q9NQC3, Q9UQ42, Q9Y293, Q9Y2Y7, Q9Y5U6
    Related
    ENSP00000337838.6, ENST00000337526.11
    Conserved Domains (1) summary
    pfam02453
    Location:1005 → 1169
    Reticulon; Reticulon

  9. NM_153828.3 → NP_722550.1  reticulon-4 isoform B

    See identical proteins and their annotated locations for NP_722550.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), also known as Foocen-M, Nogo-B, RTN-XS and RTN4-B1, lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter isoform (B), that is missing an internal segment, compared to isoform A.
    Source sequence(s)
    AF125103, AF132048, AY123250, BC016165
    Consensus CDS
    CCDS1851.1
    UniProtKB/TrEMBL
    Q6IPN0
    Related
    ENSP00000322147.7, ENST00000317610.11
    Conserved Domains (1) summary
    pfam02453
    Location:186 → 350
    Reticulon; Reticulon

  10. NM_207520.2 → NP_997403.1  reticulon-4 isoform D

    See identical proteins and their annotated locations for NP_997403.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4), also known as Foocen-m2 and RTN4-B2, lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter isoform (D), that is missing an internal segment, compared to isoform A.
    Source sequence(s)
    AF125103, AF132048, AY123250, BC016165
    Consensus CDS
    CCDS42683.1
    UniProtKB/TrEMBL
    Q6IPN0
    Related
    ENSP00000350365.4, ENST00000357732.8
    Conserved Domains (1) summary
    pfam02453
    Location:205 → 369
    Reticulon; Reticulon

  11. NM_207521.2 → NP_997404.1  reticulon-4 isoform E

    See identical proteins and their annotated locations for NP_997404.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5), also known as hRTN4-E, differs in the 5' UTR and the 5' coding region, compared to variant 1. The resulting isoform (E) has a shorter N-terminus, compared to isoform A. This variant (5), along with variants 6, 7, 8, 9, 10, and 11, encodes isoform E.
    Source sequence(s)
    AF125103, AF132048, AF333336, AY123250, BC016165
    Consensus CDS
    CCDS1852.1
    UniProtKB/TrEMBL
    Q53RF4
    Related
    ENSP00000349944.3, ENST00000357376.7
    Conserved Domains (1) summary
    pfam02453
    Location:799 → 963
    Reticulon; Reticulon

RNA

  1. NR_135829.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AY123247, BC150182, CN429712

  2. NR_135830.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AF333336, BC150182

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_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    54972189..55137831 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    54969379..55135031 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NQC3.2 GenPept UniProtKB/Swiss-Prot:Q9NQC3

Gene LinkOut

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