Free for academic non-profit institutions. Other users need a Commercial license

Aliases for RTN4 Gene

Aliases for RTN4 Gene

  • Reticulon 4 2 3 5
  • Neuroendocrine-Specific Protein C Homolog 3 4
  • Neurite Outgrowth Inhibitor 3 4
  • Foocen 3 4
  • RTN-X 3 4
  • NOGO 3 4
  • NSP 3 4
  • Neuroendocrine-Specific Protein 4
  • Neurite Growth Inhibitor 220 3
  • My043 Protein 3
  • Nogo Protein 4
  • Human NogoA 3
  • Reticulon 5 3
  • Reticulon-4 3
  • Reticulon-5 4
  • NI220/250 3
  • Nbla00271 3
  • Nbla10545 3
  • KIAA0886 4
  • RTN4-B1 3
  • RTN4-B2 3
  • NSP-CL 3
  • RTN4-A 3
  • RTN4-C 3
  • ASY 3

External Ids for RTN4 Gene

Previous GeneCards Identifiers for RTN4 Gene

  • GC02M055237
  • GC02M055386
  • GC02M055173
  • GC02M055110
  • GC02M055199

Summaries for RTN4 Gene

Entrez Gene Summary for RTN4 Gene

  • 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]

GeneCards Summary for RTN4 Gene

RTN4 (Reticulon 4) is a Protein Coding gene. Diseases associated with RTN4 include Demyelinating Disease and Pedophilia. Among its related pathways are Cytoskeleton remodeling Regulation of actin cytoskeleton by Rho GTPases and Spinal Cord Injury. GO annotations related to this gene include poly(A) RNA binding. An important paralog of this gene is RTN3.

UniProtKB/Swiss-Prot for RTN4 Gene

  • Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS. Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex (By similarity). Isoform 2 reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration. Isoform 2 and isoform 3 inhibit BACE1 activity and amyloid precursor protein processing. Induces the formation and stabilization of endoplasmic reticulum (ER) tubules (PubMed:25612671, PubMed:24262037). Regulates membrane morphogenesis in the ER by promoting tubular ER production. Influences NE expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins (PubMed:26906412).

Gene Wiki entry for RTN4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RTN4 Gene

Genomics for RTN4 Gene

Regulatory Elements for RTN4 Gene

Enhancers for RTN4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02G055002 1.4 ENCODE dbSUPER 38.8 +108.4 108418 3.1 PKNOX1 ARNT CREB3L1 ARID4B SIN3A DMAP1 YY1 SLC30A9 ZNF766 ZNF143 RTN4 CLHC1 GC02M055015 GC02M054976
GH02G054975 1.2 Ensembl ENCODE dbSUPER 44 +135.6 135571 2.2 PKNOX1 JUNB TBX21 POLR2A IKZF1 NBN TCF7 ETV6 RELB CREM RTN4 EML6 GC02M054976 GC02M055015
GH02G055005 1.3 ENCODE dbSUPER 40.1 +102.7 102657 8.2 HDGF HNRNPUL1 FOXA2 ATF1 ARNT MLX AGO1 ZFP64 SIN3A FEZF1 RTN4 CLHC1 GC02M055015 GC02M054976
GH02G055133 1.9 FANTOM5 Ensembl ENCODE dbSUPER 26.8 -21.5 -21530 2.1 PKNOX1 ATF1 ARNT YY1 ZNF766 ELK1 KLF13 CAVIN1 JUNB REST RTN4 CLHC1 RNU6-433P PPP4R3B CCDC88A GC02P055128 GC02M055160
GH02G054954 1.5 Ensembl ENCODE dbSUPER 32.4 +156.6 156636 2.3 ATF1 YY1 TCF12 ZNF766 ELK1 GATA2 CAVIN1 TBX21 ZNF592 CREB3 RTN4 CLHC1 GC02P054967 GC02P054931
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around RTN4 on UCSC Golden Path with GeneCards custom track

Genomic Location for RTN4 Gene

Chromosome:
2
Start:
54,972,187 bp from pter
End:
55,112,621 bp from pter
Size:
140,435 bases
Orientation:
Minus strand

Genomic View for RTN4 Gene

Genes around RTN4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RTN4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RTN4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RTN4 Gene

Proteins for RTN4 Gene

  • Protein details for RTN4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NQC3-RTN4_HUMAN
    Recommended name:
    Reticulon-4
    Protein Accession:
    Q9NQC3
    Secondary Accessions:
    • O94962
    • Q7L7Q5
    • Q7L7Q6
    • Q7L7Q8
    • Q8IUA4
    • Q96B16
    • Q9BXG5
    • Q9H212
    • Q9H3I3
    • Q9UQ42
    • Q9Y293
    • Q9Y2Y7
    • Q9Y5U6

    Protein attributes for RTN4 Gene

    Size:
    1192 amino acids
    Molecular mass:
    129931 Da
    Quaternary structure:
    • Binds to RTN4R. Interacts with Bcl-xl and Bcl-2. Isoform 2 binds to NGBR and RTN3. Isoform 2 and isoform 3 interact with BACE1 and BACE2. Interacts with RTN4IP1. Interacts with ATL1. Interacts with TMEM170A (PubMed:26906412). Isoform 3 interacts with TMEM33 (PubMed:25612671).
    SequenceCaution:
    • Sequence=AAD39920.1; Type=Frameshift; Positions=1149, 1156; Evidence={ECO:0000305}; Sequence=AAG43160.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAG43160.1; Type=Frameshift; Positions=684, 700; Evidence={ECO:0000305}; Sequence=BAA74909.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for RTN4 Gene

    Alternative splice isoforms for RTN4 Gene

neXtProt entry for RTN4 Gene

Post-translational modifications for RTN4 Gene

  • Ubiquitination at Lys1090 and isoforms=2, 3, 4, 5, 61171
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for RTN4 (Nogo)
  • Santa Cruz Biotechnology (SCBT) Antibodies for RTN4

No data available for DME Specific Peptides for RTN4 Gene

Domains & Families for RTN4 Gene

Protein Domains for RTN4 Gene

InterPro:
Blocks:
ProtoNet:

Graphical View of Domain Structure for InterPro Entry

Q9NQC3

UniProtKB/Swiss-Prot:

RTN4_HUMAN :
  • Three regions, residues 59-172, 544-725 and the loop 66 amino acids, between the two transmembrane domains, known as Nogo-66 loop, appear to be responsible for the inhibitory effect on neurite outgrowth and the spreading of neurons. This Nogo-66 loop, mediates also the binding of RTN4 to its receptor (By similarity).
Domain:
  • Three regions, residues 59-172, 544-725 and the loop 66 amino acids, between the two transmembrane domains, known as Nogo-66 loop, appear to be responsible for the inhibitory effect on neurite outgrowth and the spreading of neurons. This Nogo-66 loop, mediates also the binding of RTN4 to its receptor (By similarity).
genes like me logo Genes that share domains with RTN4: view

No data available for Gene Families for RTN4 Gene

Function for RTN4 Gene

Molecular function for RTN4 Gene

UniProtKB/Swiss-Prot Function:
Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS. Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex (By similarity). Isoform 2 reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration. Isoform 2 and isoform 3 inhibit BACE1 activity and amyloid precursor protein processing. Induces the formation and stabilization of endoplasmic reticulum (ER) tubules (PubMed:25612671, PubMed:24262037). Regulates membrane morphogenesis in the ER by promoting tubular ER production. Influences NE expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins (PubMed:26906412).

Gene Ontology (GO) - Molecular Function for RTN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding IDA 22658674
GO:0005515 protein binding IPI 11126360
GO:0031625 ubiquitin protein ligase binding IPI 27353365
GO:0045296 cadherin binding IDA 25468996
genes like me logo Genes that share ontologies with RTN4: view
genes like me logo Genes that share phenotypes with RTN4: view

Animal Models for RTN4 Gene

MGI Knock Outs for RTN4:

Animal Model Products

  • Taconic Biosciences Mouse Models for RTN4

CRISPR Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RTN4 Gene

Localization for RTN4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RTN4 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein. Note=Anchored to the membrane of the endoplasmic reticulum through 2 putative transmembrane domains. Co-localizes with TMEM33 at the ER sheets. {ECO:0000269 PubMed:25612671}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RTN4 gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 5
endoplasmic reticulum 5
cytoskeleton 2
mitochondrion 1
cytosol 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for RTN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IMP 14644040
GO:0005635 nuclear envelope IDA 11126360
GO:0005783 endoplasmic reticulum IEA,NAS 11126360
GO:0005789 endoplasmic reticulum membrane IDA,IEA 25612671
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with RTN4: view

Pathways & Interactions for RTN4 Gene

genes like me logo Genes that share pathways with RTN4: view

Pathways by source for RTN4 Gene

1 KEGG pathway for RTN4 Gene
1 GeneGo (Thomson Reuters) pathway for RTN4 Gene
1 Qiagen pathway for RTN4 Gene

SIGNOR curated interactions for RTN4 Gene

Activates:
Other effect:

Gene Ontology (GO) - Biological Process for RTN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process NAS 11126360
GO:0007399 nervous system development IEA --
GO:0007413 axonal fasciculation ISS --
GO:0010634 positive regulation of epithelial cell migration IMP 27353365
GO:0021801 cerebral cortex radial glia guided migration ISS --
genes like me logo Genes that share ontologies with RTN4: view

Drugs & Compounds for RTN4 Gene

(1) Additional Compounds for RTN4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with RTN4: view

Transcripts for RTN4 Gene

Unigene Clusters for RTN4 Gene

Reticulon 4:
Representative Sequences:

CRISPR Products

Alternative Splicing Database (ASD) splice patterns (SP) for RTN4 Gene

ExUns: 1 ^ 2a · 2b · 2c ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12a · 12b ^ 13 ^ 14a · 14b ^ 15a · 15b · 15c · 15d ^ 16 ^
SP1: - - - - - - - - - - - - - - - -
SP2: - - - - - - - - - - - - -
SP3: - - - - - - - - - - -
SP4: - - - - - - - - -
SP5: - - - - - - - -
SP6: - - - - - - -
SP7: - - - - - -
SP8: - - - - - - - - - - - -
SP9: - - - - - - - - - - - - -
SP10: - - - - - - - - - - -
SP11: - - - -
SP12: - - -
SP13: - - - - -
SP14: - - - - - -
SP15: - -
SP16:
SP17:
SP18:

ExUns: 17a · 17b · 17c · 17d
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:

Relevant External Links for RTN4 Gene

GeneLoc Exon Structure for
RTN4
ECgene alternative splicing isoforms for
RTN4

Expression for RTN4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for RTN4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for RTN4 Gene



Protein tissue co-expression partners for RTN4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of RTN4 Gene:

RTN4

SOURCE GeneReport for Unigene cluster for RTN4 Gene:

Hs.637850

mRNA Expression by UniProt/SwissProt for RTN4 Gene:

Q9NQC3-RTN4_HUMAN
Tissue specificity: Isoform 1 is specifically expressed in brain and testis and weakly in heart and skeletal muscle. Isoform 2 is widely expressed except for the liver. Isoform 3 is expressed in brain, skeletal muscle and adipocytes. Isoform 4 is testis-specific.

Evidence on tissue expression from TISSUES for RTN4 Gene

  • Muscle(5)
  • Nervous system(5)
  • Liver(4.7)
  • Blood(4.5)
  • Eye(4.4)
  • Skin(4.4)
  • Kidney(4.3)
  • Lung(4.2)
  • Pancreas(4.1)
  • Heart(2.7)
  • Adrenal gland(2.6)
  • Intestine(2.4)
  • Bone(2.2)
  • Gall bladder(2.1)
genes like me logo Genes that share expression patterns with RTN4: view

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for RTN4 Gene

Orthologs for RTN4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for RTN4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RTN4 35
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia RTN4 34 35
  • 91 (n)
dog
(Canis familiaris)
Mammalia RTN4 34 35
  • 88.51 (n)
mouse
(Mus musculus)
Mammalia Rtn4 34 16 35
  • 83.56 (n)
rat
(Rattus norvegicus)
Mammalia Rtn4 34
  • 83.28 (n)
oppossum
(Monodelphis domestica)
Mammalia RTN4 35
  • 69 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RTN4 35
  • 65 (a)
OneToOne
chicken
(Gallus gallus)
Aves RTN4 35
  • 73 (a)
OneToOne
LOC101749579 34
  • 60.49 (n)
lizard
(Anolis carolinensis)
Reptilia RTN4 35
  • 45 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rtn4 34
  • 58.06 (n)
Str.386 34
African clawed frog
(Xenopus laevis)
Amphibia MGC68489 34
zebrafish
(Danio rerio)
Actinopterygii rtn4a 35
  • 51 (a)
OneToOne
Dr.24718 34
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8546 34
fruit fly
(Drosophila melanogaster)
Insecta Rtnl1 35
  • 27 (a)
ManyToMany
Rtnl2 35
  • 22 (a)
ManyToMany
CG42853 35
  • 18 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea ret-1 35
  • 7 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes RTN2 37
sea squirt
(Ciona savignyi)
Ascidiacea CSA.10170 35
  • 33 (a)
OneToMany
Species where no ortholog for RTN4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for RTN4 Gene

ENSEMBL:
Gene Tree for RTN4 (if available)
TreeFam:
Gene Tree for RTN4 (if available)

Paralogs for RTN4 Gene

Paralogs for RTN4 Gene

genes like me logo Genes that share paralogs with RTN4: view

Variants for RTN4 Gene

Sequence variations from dbSNP and Humsavar for RTN4 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
VAR_035904 A colorectal cancer sample
rs1000037017 -- 54,975,267(+) CTTTG(A/C)AGGAT intron-variant
rs1000041744 -- 55,118,021(+) TGTTT(A/G)GGATT intron-variant
rs1000052566 -- 55,081,909(+) CCTGC(C/T)TTTTT intron-variant
rs1000064918 -- 55,035,168(+) CCACT(A/G)CCAAT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RTN4 Gene

Variant ID Type Subtype PubMed ID
esv2474783 CNV deletion 19546169
esv2517082 CNV deletion 19546169
esv2720078 CNV deletion 23290073
esv3340657 CNV insertion 20981092
nsv582029 CNV loss 21841781
nsv834069 CNV loss 17160897
nsv953127 CNV duplication 24416366

Variation tolerance for RTN4 Gene

Residual Variation Intolerance Score: 35.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.11; 80.53% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for RTN4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
RTN4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RTN4 Gene

Disorders for RTN4 Gene

MalaCards: The human disease database

(13) MalaCards diseases for RTN4 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
demyelinating disease
  • demyelinating disorder
pedophilia
  • paedophilia
disease of mental health
  • mental health
specific developmental disorder
dependent personality disorder
- elite association - COSMIC cancer census association via MalaCards
Search RTN4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for RTN4

Genetic Association Database (GAD)
RTN4
Human Genome Epidemiology (HuGE) Navigator
RTN4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
RTN4
genes like me logo Genes that share disorders with RTN4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RTN4 Gene

Publications for RTN4 Gene

  1. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. (PMID: 10667797) GrandPre T. … Strittmatter S.M. (Nature 2000) 2 3 4 22 64
  2. The association between dilated cardiomyopathy and RTN4 3'UTR insertion/deletion polymorphisms. (PMID: 18948092) Zhou B. … Zhang L. (Clin. Chim. Acta 2009) 3 22 46 64
  3. Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells. (PMID: 16835300) Miao R.Q. … Sessa W.C. (Proc. Natl. Acad. Sci. U.S.A. 2006) 3 4 22 64
  4. Gender-specific association of insertion/deletion polymorphisms in the nogo gene and chronic schizophrenia. (PMID: 15953657) Tan E.C. … Teo Y.Y. (Brain Res. Mol. Brain Res. 2005) 3 22 46 64
  5. Nogo CAA 3'UTR Insertion polymorphism is not associated with Schizophrenia nor with bipolar disorder. (PMID: 15820318) GregA^rio S.P. … Dias-Neto E. (Schizophr. Res. 2005) 3 22 46 64

Products for RTN4 Gene

  • Addgene plasmids for RTN4

Sources for RTN4 Gene

Content
Loading form....