Human Gene RTN4 (uc002rye.3) Description and Page Index
  Description: Homo sapiens reticulon 4 (RTN4), transcript variant 1, mRNA.
RefSeq Summary (NM_020532): 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].
Transcript (Including UTRs)
   Position: hg19 chr2:55,199,327-55,277,734 Size: 78,408 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg19 chr2:55,200,292-55,277,436 Size: 77,145 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr2:55,199,327-55,277,734)mRNA (may differ from genome)Protein (1192 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDHuman Cortex Gene ExpressionLynx
MGIneXtProtOMIMPubMedReactomeStanford SOURCE

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Reticulon-4; AltName: Full=Foocen; AltName: Full=Neurite outgrowth inhibitor; Short=Nogo protein; AltName: Full=Neuroendocrine-specific protein; Short=NSP; AltName: Full=Neuroendocrine-specific protein C homolog; AltName: Full=RTN-x; AltName: Full=Reticulon-5;
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.
SUBUNIT: 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.
INTERACTION: Q8WXF7:ATL1; NbExp=2; IntAct=EBI-715972, EBI-2410266;
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. Note=Anchored to the membrane of the endoplasmic reticulum through 2 putative transmembrane domains.
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.
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).
SIMILARITY: Contains 1 reticulon domain.
SEQUENCE CAUTION: Sequence=AAD39920.1; Type=Frameshift; Positions=1149, 1156; Sequence=AAG43160.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAG43160.1; Type=Frameshift; Positions=684, 700; Sequence=BAA74909.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="";
WEB RESOURCE: Name=Protein Spotlight; Note=Nerve regrowth: nipped by a no-go - Issue 69 of April 2006; URL="";
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): RTN4
CDC HuGE Published Literature: RTN4
Positive Disease Associations: Cholesterol, HDL , Hypertension , Lipids , obesity (extreme) , schizophrenia , Triglycerides
Related Studies:
  1. Cholesterol, HDL
    , , . [PubMed 0]
  2. Cholesterol, HDL
    , , . [PubMed 0]
  3. Cholesterol, HDL
    , , . [PubMed 0]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: RTN4
Diseases sorted by gene-association score: demyelinating disease (3), alzheimer disease (2), pedophilia (2), disease of mental health (2), amyotrophic lateral sclerosis 1 (2), specific developmental disorder (2), schizophrenia (2), partial fetal alcohol syndrome (1), dependent personality disorder (1), paraphilia disorder (1), space motion sickness (1), separation anxiety disorder (1), ideomotor apraxia (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D001564 Benzo(a)pyrene
  • D013629 Tamoxifen
  • D013749 Tetrachlorodibenzodioxin
  • C006253 pirinixic acid
  • C517041 (4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)
  • C028474 1,4-bis(2-(3,5-dichloropyridyloxy))benzene
  • C023514 2,6-dinitrotoluene
  • C030370 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • D015127 9,10-Dimethyl-1,2-benzanthracene
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 124.04 RPKM in Brain - Frontal Cortex (BA9)
Total median expression: 2836.30 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -136.60298-0.458 Picture PostScript Text
3' UTR -246.38965-0.255 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003388 - Reticulon

Pfam Domains:
PF02453 - Reticulon

Protein Data Bank (PDB) 3-D Structure
MuPIT help



ModBase Predicted Comparative 3D Structure on Q9NQC3
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserNo orthologNo ortholog
Gene DetailsGene Details Gene Details  
Gene SorterGene Sorter Gene Sorter  
 Protein SequenceProtein SequenceProtein Sequence  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003723 RNA binding
GO:0005515 protein binding
GO:0031625 ubiquitin protein ligase binding
GO:0045296 cadherin binding

Biological Process:
GO:0001525 angiogenesis
GO:0006915 apoptotic process
GO:0007399 nervous system development
GO:0007413 axonal fasciculation
GO:0010634 positive regulation of epithelial cell migration
GO:0021801 cerebral cortex radial glia guided migration
GO:0030308 negative regulation of cell growth
GO:0030334 regulation of cell migration
GO:0030517 negative regulation of axon extension
GO:0033601 positive regulation of mammary gland epithelial cell proliferation
GO:0042981 regulation of apoptotic process
GO:0048694 positive regulation of collateral sprouting of injured axon
GO:0050771 negative regulation of axonogenesis
GO:0050821 protein stabilization
GO:0051292 nuclear pore complex assembly
GO:0051897 positive regulation of protein kinase B signaling
GO:0051960 regulation of nervous system development
GO:0060317 cardiac epithelial to mesenchymal transition
GO:0071277 cellular response to calcium ion
GO:0071786 endoplasmic reticulum tubular network organization
GO:0071787 endoplasmic reticulum tubular network assembly
GO:1903860 negative regulation of dendrite extension
GO:1905552 positive regulation of protein localization to endoplasmic reticulum
GO:1905580 positive regulation of ERBB3 signaling pathway
GO:1990809 endoplasmic reticulum tubular network membrane organization
GO:2000172 regulation of branching morphogenesis of a nerve

Cellular Component:
GO:0005622 intracellular
GO:0005635 nuclear envelope
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005886 plasma membrane
GO:0014069 postsynaptic density
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030176 integral component of endoplasmic reticulum membrane
GO:0030424 axon
GO:0042995 cell projection
GO:0043025 neuronal cell body
GO:0044294 dendritic growth cone
GO:0071782 endoplasmic reticulum tubular network
GO:0098826 endoplasmic reticulum tubular network membrane

-  Descriptions from all associated GenBank mRNAs
  KJ906268 - Synthetic construct Homo sapiens clone ccsbBroadEn_15938 RTN4 gene, encodes complete protein.
AF087901 - Homo sapiens reticulon 4c mRNA, complete cds.
AF177332 - Homo sapiens clone SP1507 unknown mRNA.
AF132048 - Homo sapiens foocen-s mRNA, complete cds.
JA482188 - Sequence 171 from Patent WO2011072091.
JE980480 - Sequence 171 from Patent EP2862929.
AY102276 - Homo sapiens RTN4 isoform C (RTN4) mRNA, complete cds; alternatively spliced.
AY123250 - Homo sapiens RTN4 isoform G (RTN4) mRNA, complete cds; alternatively spliced.
AY123249 - Homo sapiens RTN4 isoform F (RTN4) mRNA, complete cds; alternatively spliced.
JA482190 - Sequence 173 from Patent WO2011072091.
JE980482 - Sequence 173 from Patent EP2862929.
AY123248 - Homo sapiens RTN4 isoform E (RTN4) mRNA, complete cds; alternatively spliced.
AY123247 - Homo sapiens RTN4 isoform D (RTN4) mRNA, complete cds; alternatively spliced.
AF148537 - Homo sapiens reticulon 4a mRNA, complete cds.
AF148538 - Homo sapiens reticulon 4b mRNA, complete cds.
AF132047 - Homo sapiens foocen-m mRNA, complete cds.
AY102277 - Homo sapiens RTN4 isoform B1 (RTN4) mRNA, complete cds; alternatively spliced.
AY102278 - Homo sapiens RTN4 isoform B2 (RTN4) mRNA, complete cds; alternatively spliced.
AY102279 - Homo sapiens RTN4 isoform A (RTN4) mRNA, complete cds; alternatively spliced.
BC150182 - Homo sapiens reticulon 4, mRNA (cDNA clone MGC:164945 IMAGE:40148210), complete cds.
BC152555 - Homo sapiens reticulon 4, mRNA (cDNA clone MGC:165109 IMAGE:40148984), complete cds.
AY123246 - Homo sapiens RTN4 isoform Ab (RTN4) mRNA, complete cds; alternatively spliced.
JA482186 - Sequence 169 from Patent WO2011072091.
JA482187 - Sequence 170 from Patent WO2011072091.
JA482189 - Sequence 172 from Patent WO2011072091.
JE980478 - Sequence 169 from Patent EP2862929.
JE980479 - Sequence 170 from Patent EP2862929.
JE980481 - Sequence 172 from Patent EP2862929.
AY123245 - Homo sapiens RTN4 isoform Aa (RTN4) mRNA, complete cds; alternatively spliced.
AK172726 - Homo sapiens cDNA PSEC0023 fis, clone: NT2RP1000386.
AB015639 - Homo sapiens ASY mRNA, complete cds.
BC014366 - Homo sapiens reticulon 4, mRNA (cDNA clone IMAGE:3933041), complete cds.
AF125103 - Homo sapiens neuroendocrine specific protein c homolog mRNA, complete cds.
AF077050 - Homo sapiens neuroendocrine-specific protein C homolog mRNA, complete cds.
JD410376 - Sequence 391400 from Patent EP1572962.
JD059273 - Sequence 40297 from Patent EP1572962.
JD038323 - Sequence 19347 from Patent EP1572962.
BC131571 - Homo sapiens cDNA clone IMAGE:40108446.
BC007109 - Homo sapiens reticulon 4, mRNA (cDNA clone IMAGE:4291127), complete cds.
BC001035 - Homo sapiens reticulon 4, mRNA (cDNA clone IMAGE:3139770), complete cds.
AB073351 - Homo sapiens primary neuroblastoma mRNA for NOGO-A, partial cds, clone:Nbla00271.
BC010737 - Homo sapiens reticulon 4, mRNA (cDNA clone IMAGE:3901353), complete cds.
BC071848 - Homo sapiens reticulon 4, mRNA (cDNA clone IMAGE:4635625), complete cds.
BC152425 - Homo sapiens reticulon 4, mRNA (cDNA clone MGC:176660 IMAGE:8862539), complete cds.
BC026788 - Homo sapiens reticulon 4, mRNA (cDNA clone IMAGE:3862911), complete cds.
BC012335 - Homo sapiens cDNA clone IMAGE:3510627, **** WARNING: chimeric clone ****.
BC016165 - Homo sapiens reticulon 4, mRNA (cDNA clone IMAGE:3505850), complete cds.
BC068991 - Homo sapiens reticulon 4, mRNA (cDNA clone IMAGE:4634289), complete cds.
AF063601 - Homo sapiens brain my043 protein mRNA, complete cds.
AK130812 - Homo sapiens cDNA FLJ27302 fis, clone TMS04776.
AB020693 - Homo sapiens KIAA0886 mRNA for KIAA0886 protein.
AX195249 - Sequence 5 from Patent WO0151520.
AK129806 - Homo sapiens cDNA FLJ26295 fis, clone DMC07157.
AK075039 - Homo sapiens cDNA FLJ90558 fis, clone OVARC1001030.
AK090714 - Homo sapiens cDNA FLJ33395 fis, clone BRACE2007064.
BC012619 - Homo sapiens reticulon 4, mRNA (cDNA clone IMAGE:4082756), complete cds.
AF333336 - Homo sapiens testis specific reticulon 5 protein mRNA, complete cds.
AB040462 - Homo sapiens mRNA for RTN-xL, complete cds.
AB040463 - Homo sapiens mRNA for RTN-xS, complete cds.
JD432925 - Sequence 413949 from Patent EP1572962.
DL491385 - Novel nucleic acids.
DL490013 - Novel nucleic acids.
DQ598072 - Homo sapiens piRNA piR-36138, complete sequence.
AJ251385 - Homo sapiens mRNA for Nogo-C protein (Nogo gene).
DQ778739 - Homo sapiens Nogo-C (NOGOC) mRNA, complete cds.
AF320999 - Homo sapiens Nogo-A protein short form mRNA, complete cds, alternatively spliced.
AJ251383 - Homo sapiens mRNA for Nogo-A protein (Nogo gene).
AJ251384 - Homo sapiens mRNA for Nogo-B protein (Nogo gene).
KJ906267 - Synthetic construct Homo sapiens clone ccsbBroadEn_15937 RTN4 gene, encodes complete protein.
KJ894399 - Synthetic construct Homo sapiens clone ccsbBroadEn_03793 RTN4 gene, encodes complete protein.
KJ894400 - Synthetic construct Homo sapiens clone ccsbBroadEn_03794 RTN4 gene, encodes complete protein.
AM392753 - Synthetic construct Homo sapiens clone IMAGE:100003033 for hypothetical protein (RTN4 gene).
AM393280 - Synthetic construct Homo sapiens clone IMAGE:100003034 for hypothetical protein (RTN4 gene).
AB384033 - Synthetic construct DNA, clone: pF1KSDA0886, Homo sapiens RTN4 gene for reticulon-4, complete cds, without stop codon, in Flexi system.
AM393122 - Synthetic construct Homo sapiens clone IMAGE:100002775 for hypothetical protein (RTN4 gene).
AM393537 - Synthetic construct Homo sapiens clone IMAGE:100002776 for hypothetical protein (RTN4 gene).
BC139928 - Synthetic construct Homo sapiens clone IMAGE:100002775, MGC:165147 reticulon 4 (RTN4) mRNA, encodes complete protein.
AM393104 - Synthetic construct Homo sapiens clone IMAGE:100002769 for hypothetical protein (RTN4 gene).
AM393557 - Synthetic construct Homo sapiens clone IMAGE:100002793 for hypothetical protein (RTN4 gene).
AK093785 - Homo sapiens cDNA FLJ36466 fis, clone THYMU2015409.
CQ873854 - Sequence 273 from Patent WO2004076622.
DD413691 - Regulation of Mammalian Cells.
AB073359 - Homo sapiens primary neuroblastoma mRNA for NOGO-A, partial cds, clone:Nbla10545.
AK098385 - Homo sapiens cDNA FLJ25519 fis, clone CBR06737, highly similar to Homo sapiens mRNA for Nogo-A protein (Nogo gene).
AK302741 - Homo sapiens cDNA FLJ54947 complete cds, highly similar to Reticulon-4.
CU687182 - Synthetic construct Homo sapiens gateway clone IMAGE:100023156 5' read RTN4 mRNA.
DL491540 - Novel nucleic acids.
DL490145 - Novel nucleic acids.
JD126928 - Sequence 107952 from Patent EP1572962.
JD371792 - Sequence 352816 from Patent EP1572962.
JD395086 - Sequence 376110 from Patent EP1572962.
JD099221 - Sequence 80245 from Patent EP1572962.
JD246359 - Sequence 227383 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9NQC3 (Reactome details) participates in the following event(s):

R-HSA-193655 Myelin components can interact with p75NTR:NgR:LINGO1
R-HSA-9012761 The p75NTR:NgR:MDGI binds RHOA-GDI
R-HSA-193696 The p75NTR:NgR:MDGI complex reduces RHOA-GDI activity, displacing RHOA
R-HSA-193634 Axonal growth inhibition (RHOA activation)
R-HSA-193697 p75NTR regulates axonogenesis
R-HSA-193704 p75 NTR receptor-mediated signalling
R-HSA-73887 Death Receptor Signalling
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: KIAA0886, My043, NM_020532, NOGO, NP_997404, O94962, Q7L7Q5, Q7L7Q6, Q7L7Q8, Q8IUA4, Q96B16, Q9BXG5, Q9H212, Q9H3I3, Q9NQC3, Q9UQ42, Q9Y293, Q9Y2Y7, Q9Y5U6, RTN4_HUMAN, SP1507
UCSC ID: uc002rye.3
RefSeq Accession: NM_020532
Protein: Q9NQC3 (aka RTN4_HUMAN)
CCDS: CCDS42684.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_020532.4
exon count: 9CDS single in 3' UTR: no RNA size: 4871
ORF size: 3579CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 7355.00frame shift in genome: no % Coverage: 99.40
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.