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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
    mouse all
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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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous