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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

RTN4 Gene

protein-coding GIFtS: 68
GCID: GC02M055199

Reticulon 4

Alzheimer's & Parkinson's Diseases Congress

32 related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
About This Section

Aliases
Reticulon 4¹ ²		RTN4-B1²
NOGO² ³ ⁵		RTN4-B2²
Neurite Outgrowth Inhibitor² ³		RTN4-C²
Neuroendocrine-Specific Protein C Homolog² ³		foocen²
NSP² ³		Human NogoA²
ASY²		My043 Protein²
NI220/250²		Neurite Growth Inhibitor 220²
NOGO-A²		Reticulon 5²
NOGOC²		reticulon-4²
NSP-CL²		Foocen³
Nbla00271²		KIAA0886³
Nbla10545²		RTN-x³
Nogo-B²		Reticulon-5³
Nogo-C²		Neuroendocrine-Specific Protein³
RTN-X²		Nogo Protein³
RTN4-A²

External Ids:	HGNC: 14085¹	Entrez Gene: 57142²	Ensembl: ENSG00000115310⁷	OMIM: 604475⁵	UniProtKB: Q9NQC3³

Export aliases for RTN4 gene to outside databases

Previous GC identifers: GC02M055237 GC02M055386 GC02M055173 GC02M055110 GC02M054934

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

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 pathological gambling, and ventricular septal defect, and among its related super-pathways are p75NTR regulates axonogenesis and Development MAG-dependent inhibition of neurite outgrowth. GO annotations related to this gene include protein binding. An important paralog of this gene is RTN3.

UniProtKB/Swiss-Prot: RTN4_HUMAN, Q9NQC3

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

Gene Wiki entry for RTN4 (Reticulon 4) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000002.11 NT_022184.15 NC_018913.2

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the RTN4 gene promoter:
POU2F1 POU2F1a C/EBPalpha
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 10): RTN4 promoter sequence

Search SABiosciences Chromatin IP Primers for RTN4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat RTN4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2p16.3 Ensembl cytogenetic band: 2p16.1 HGNC cytogenetic band: 2p14-p13

RTN4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RTN4 gene location

GeneLoc information about chromosome 2 GeneLoc Exon Structure

GeneLoc location for GC02M055199: view genomic region (about GC identifiers)

Start:	55,199,325 bp from pter	End:	55,339,757 bp from pter
Size:	140,433 bases	Orientation:	minus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: RTN4_HUMAN, Q9NQC3 (See protein sequence)

Recommended Name: Reticulon-4

Size: 1192 amino acids; 129931 Da

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

Subcellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein. Note=Anchored to the membrane of the

endoplasmic reticulum through 2 putative transmembrane domains

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;

2 PDB 3D structures from and Proteopedia for RTN4:

2G31 (3D)

2JV5 (3D)

Secondary accessions: O94962 Q7L7Q5 Q7L7Q6 Q7L7Q8 Q8IUA4 Q96B16 Q9BXG5 Q9H212 Q9H3I3 Q9UQ42 Q9Y293

Q9Y2Y7 Q9Y5U6

Alternative splicing: 6 isoforms: Q9NQC3-1 Q9NQC3-2 Q9NQC3-3 Q9NQC3-4 Q9NQC3-5 Q9NQC3-6

Explore the universe of human proteins at neXtProt for RTN4: NX_Q9NQC3

Explore proteomics data for RTN4 at MOPED

Post-translational modifications:

View modification sites using PhosphoSitePlus

View neXtProt modification sites for NX_Q9NQC3

RTN4 Protein expression data from MOPED¹, PaxDb² and MAXQB³ : About this image

REFSEQ proteins (5 alternative transcripts):

NP_008939.1 NP_065393.1 NP_722550.1 NP_997403.1 NP_997404.1

ENSEMBL proteins:

ENSP00000378107 ENSP00000384471 ENSP00000349944 ENSP00000337838 ENSP00000322147

ENSP00000350365 ENSP00000378109 ENSP00000385650 ENSP00000397808 ENSP00000411628

ENSP00000384825 ENSP00000346465

Reactome Protein details: Q9NQC3
Human Recombinant Protein Products for RTN4:

	Browse Purified and Recombinant Proteins at EMD Millipore
	R&D Systems Recombinant & Natural Proteins for RTN4 (Nogo-A)
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Proteins for RTN4 OriGene Protein Over-expression Lysate for RTN4 OriGene MassSpec for RTN4 OriGene Custom Protein Services for RTN4
	GenScript Custom Purified and Recombinant Proteins Services for RTN4
	Novus Biologicals RTN4 Proteins Novus Biologicals RTN4 Lysates
	Sino Biological Recombinant Protein for RTN4 Browse Sino Biological Cell Lysates
	Browse ProSpec Recombinant Proteins
	Cloud-Clone Corp. Proteins for RTN4

Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005635	nuclear envelope	IDA	11126360
GO:0005783	endoplasmic reticulum	NAS	11126360
GO:0005886	plasma membrane	TAS	--
GO:0030176	integral to endoplasmic reticulum membrane	IDA	10667797
GO:0042995	cell projection	IEA	--

RTN4 for ontologies About GeneDecksing

RTN4 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of RTN4
	R&D Systems Antibodies for RTN4 (Nogo-A, Nogo-B, Nogo-C)
	OriGene Antibodies for RTN4 OriGene Custom Antibody Services for RTN4
	GenScript Custom Superior Antibodies Services for RTN4
	Novus Biologicals RTN4 Antibodies
	Abcam antibodies for RTN4
	Cloud-Clone Corp. Antibodies for RTN4
	ThermoFisher Antibodies for RTN4
	LSBio Antibodies in human, mouse, rat for RTN4

Assay Products for RTN4:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for RTN4
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for RTN4
	Browse Enzo Life Sciences for kits & assays
	Cloud-Clone Corp. ELISAs for RTN4 Cloud-Clone Corp. CLIAs for RTN4

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

1 InterPro protein domain:

IPR003388 Reticulon

Graphical View of Domain Structure for InterPro Entry Q9NQC3

ProtoNet protein and cluster: Q9NQC3

1 Blocks protein domain: IPB003388 Reticulon

UniProtKB/Swiss-Prot: RTN4_HUMAN, Q9NQC3

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

RTN4 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: RTN4_HUMAN, Q9NQC3

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

Gene Ontology (GO): 1 molecular function term (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005515	protein binding	IPI	11126360

RTN4 for ontologies About GeneDecksing

Phenotypes:
4 MGI mutant phenotypes (inferred from 8 alleles) (MGI details for Rtn4):

cellular

mortality/aging

nervous system

normal

RTN4 for phenotypes About GeneDecksing

Animal Models:
Mouse knock-outs for RTN4: Rtn4^tm1Schw Rtn4^tm2.1Matl Rtn4^tm2Matl

inGenious Targeting Laboratory - Custom generated mouse model solutions for RTN4

inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for RTN4

miRNA Products:		miRTarBase miRNAs that target RTN4: hsa-mir-16 (MIRT001421), hsa-mir-21 (MIRT000167)


		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat RTN4
		8/19 QIAGEN miScript miRNA Assays for microRNAs that regulate RTN4 (see all 19):
		hsa-miR-4318 hsa-miR-15a hsa-miR-503 hsa-miR-3692 hsa-miR-424 hsa-miR-195 hsa-miR-497* hsa-miR-15b

		SwitchGear 3'UTR luciferase reporter plasmid: RTN4 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene RNAi products in human, mouse, rat for RTN4
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat RTN4
		Sirion Biotech Custom design and validation of potent shRNA sequences against RTN4

Gene Editing Products:			DNA2.0 Custom Protein Engineering Service for RTN4
			Sirion Biotech Customized adenovirus for overexpression of RTN4 Customized adenovirus for potent knockdown of RTN4

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene clones in human, mouse for RTN4 (see all 32) OriGene ORF clones in mouse, rat for RTN4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 5): RTN4 (NM_020532)
		Sino Biological Human cDNA Clone for RTN4
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for RTN4
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat RTN4

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for RTN4
		Search LifeMap BioReagents cell lines for RTN4
		Sirion Biotech Customized stable knockdown cell line services for RTN4 Customized inducible knockdown cell line services for RTN4 Customized stable overexpressing cell line services for RTN4 Customized inducible overexpressing cell line services for RTN4

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for RTN4

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
About This Section

SuperPaths for RTN4 About (see all 8)

See pathways by source

SuperPath

Contained pathways About

Axonal growth inhibition (RHOA activation)

Axonal growth inhibition (RHOA activation)

0.90

p75NTR regulates axonogenesis

0.90

Development MAG-dependent inhibition of neurite outgrowth

Development MAG-dependent inhibition of neurite outgrowth

0.87

Cell death signalling via NRAGE, NRIF and NADE

p75 NTR receptor-mediated signalling

0.73

Signaling by FGFR

Signalling by NGF

0.71

Signaling by GPCR

Signal Transduction

0.55

Pathways by source See SuperPaths
Show all pathways

1 EMD Millipore Pathway for RTN4

Development MAG-dependent inhibition of neurite outgrowth

1 Downloadable PowerPoint Slide of QIAGEN Pathway Central Maps for RTN4

NgR-p75(NTR)-Mediated Signaling

1 GeneGo (Thomson Reuters) Pathway for RTN4

Development MAG-dependent inhibition of neurite outgrowth

2 BioSystems Pathways for RTN4

	Spinal Cord Injury
	p75(NTR)-mediated signaling

5 Reactome Pathways for RTN4

	Axonal growth inhibition (RHOA activation)
	Signal Transduction
	p75NTR regulates axonogenesis
	Signalling by NGF
	p75 NTR receptor-mediated signalling

RTN4 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for RTN4

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/67 Interacting proteins for RTN4 (Q9NQC3^{1, 2, 3} ENSP00000337838⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 67)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
ENSG00000236693	P04440²^,³, ENSP00000414196⁴	MINT-8258153 I2D: score=2 STRING: ENSP00000414196
ENSG00000237710	P04440²^,³, ENSP00000389288⁴	MINT-8258153 I2D: score=2 STRING: ENSP00000389288
ENSG00000215048	P04440²^,³	MINT-8258153 I2D: score=2
ENSG00000226826	P04440²^,³	MINT-8258153 I2D: score=2
ENSG00000230763	P04440²^,³	MINT-8258153 I2D: score=2

About this table

Gene Ontology (GO): 5/16 biological process terms (GO ID links to tree view) (see all 16): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001525	angiogenesis	IEA	--
GO:0006915	apoptotic process	NAS	11126360
GO:0007399	nervous system development	--	--
GO:0007413	axonal fasciculation	ISS	--
GO:0021801	cerebral cortex radial glia guided migration	ISS	--

RTN4 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, IUPHAR, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

RTN4 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for RTN4

1 Novoseek inferred chemical compound relationship for RTN4 gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
ddvp	58	1	17029193 (1)

Search CenterWatch for drugs/clinical trials and news about RTN4

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, Sirion Biotech, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for RTN4 gene (5 alternative transcripts):

NM_007008.2 NM_020532.4 NM_153828.2 NM_207520.1 NM_207521.1

Unigene Cluster for RTN4:

Reticulon 4

Hs.637850 [show with all ESTs]

Unigene Representative Sequence: NM_020532

16 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000394609(uc002ryc.3) ENST00000405240 ENST00000357376(uc002ryd.3)

ENST00000337526(uc002rye.3) ENST00000317610(uc002ryg.3) ENST00000357732(uc002ryf.3)

ENST00000394611 ENST00000404909 ENST00000486085 ENST00000491592 ENST00000485749

ENST00000438462 ENST00000427710 ENST00000461004 ENST00000402434 ENST00000354474

miRNA Products:
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat RTN4
		8/19 QIAGEN miScript miRNA Assays for microRNAs that regulate RTN4 (see all 19):
		hsa-miR-4318 hsa-miR-15a hsa-miR-503 hsa-miR-3692 hsa-miR-424 hsa-miR-195 hsa-miR-497* hsa-miR-15b

		SwitchGear 3'UTR luciferase reporter plasmid: RTN4 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene RNAi products in human, mouse, rat for RTN4
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat RTN4
		Sirion Biotech Custom design and validation of potent shRNA sequences against RTN4

Clone Products:		OriGene clones in human, mouse for RTN4 (see all 32) OriGene ORF clones in mouse, rat for RTN4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 5): RTN4 (NM_020532)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for RTN4
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat RTN4

Primer Products:		OriGene qPCR primer pairs and template standards for RTN4 OriGene qSTAR qPCR primer pairs in human, mouse for RTN4
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat RTN4
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat RTN4
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat RTN4

Additional mRNA sequence:

AB015639.1 AB020693.1 AB040462.1 AB040463.1 AB073351.1 AB073359.1 AF063601.1 AF077050.1

AF087901.1 AF125103.1 AF132047.1 AF132048.1 AF148537.1 AF148538.1 AF177332.1 AF320999.1

AF333336.1 AJ251383.1 AJ251384.1 AJ251385.1 AK075039.1 AK098385.1 AK129806.1 AK130812.1

AK172726.1 AK302741.1 AY102276.1 AY102277.1 AY102278.1 AY102279.1 AY123245.1 AY123246.1

AY123247.1 AY123248.1 AY123249.1 AY123250.1 BC001035.2 BC007109.1 BC010737.1 BC012619.1

BC014366.1 BC016165.1 BC026788.1 BC068991.1 BC071848.1 BC150182.1 BC152425.1 BC152555.1

DQ778739.1

24/70 DOTS entries (see all 70):

DT.87018236 DT.92057768 DT.91855184 DT.100039375 DT.97862663 DT.95148397 DT.100889622 DT.97776594

DT.100039374 DT.100889645 DT.100039372 DT.121021010 DT.100889631 DT.420660 DT.100889638 DT.100889649

DT.100889641 DT.100889621 DT.121021012 DT.408266 DT.95128616 DT.95329023 DT.100889636 DT.102838873

24/1507 AceView cDNA sequences (see all 1507):

AA746210 AA370616 CB164794 AA192937 W19399 BF448757 BQ638521 AA331600

BF591729 CB162885 AJ251384 W73282 CB108617 BU729639 AU104978 AY123247

BU952509 W21129 CB133824 AI217084 BM709363 AA058672 W95807 AL533461

GeneLoc Exon Structure

5/18 Alternative Splicing Database (ASD) splice patterns (SP) for RTN4 (see all 18) About this scheme

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:																			-		-						-		-		-								-				-		-

ExUns:	17a	·	17b	·	17c	·	17d
SP1:
SP2:
SP3:
SP4:
SP5:

ECgene alternative splicing isoforms for RTN4

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

RTN4 expression in normal human tissues (normalized intensities) RTN4 embryonic expression: see
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: AAATGCCACA

About this image

RTN4 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database

5/6 selected tissues (see all 6) fully expand


Brain (Nervous System) fully expand to see all 25 entries
Thalamus
Septum

Spinal Cord (Nervous System) fully expand to see all 3 entries
Dorsal Horn

Peripheral Nervous System (Nervous System) fully expand to see all 2 entries
colon ; peripheral nerve/ganglion
spinal/ganglion/dorsal root ganglion

Testis (Reproductive System)
testis ; cells in seminiferus ducts

Lower Urinary Tract (Urinary System)
visceral organ/urethra of male/pelvic urethra of male

See RTN4 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for RTN4

SOURCE GeneReport for Unigene cluster: Hs.637850

UniProtKB/Swiss-Prot: RTN4_HUMAN, Q9NQC3

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

SABiosciences Expression via Pathway-Focused PCR Arrays including RTN4:

Neurogenesis in human mouse rat

Nephrotoxicity in human mouse rat

Apoptosis 384HT in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for RTN4 gene from 5/15 species (see all 15) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Rtn4^{1 , 5}	reticulon 4^{1, 5}	83.97(n)¹ 78.32(a)¹		11 (16.79 cM)⁵ 68585¹ NM_194054.3¹ NP_918943.1¹ 29692947⁵
chicken (Gallus gallus)	Aves	RTN4¹	reticulon 4	65.24(n) 54.37(a)		378790 XM_003640893.1 XP_003640941.1
lizard (Anolis carolinensis)	Reptilia	RTN4⁶	Uncharacterized protein	47(a)	1 ↔ 1	1(263834474-263901082)
African clawed frog (Xenopus laevis)	Amphibia	MGC68489²	hypothetical protein MGC68489	78.12(n)		BC059960.1
zebrafish (Danio rerio)	Actinopterygii	Dr.24718²	Transcribed sequence with weak similarity to protein more	74.33(n)		57038777

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

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for RTN4 gene

RTN3² RTN1² RTN2²

6 SIMAP similar genes for RTN4 using alignment to 10 protein entries: RTN4_HUMAN (see all proteins):

NOGOC Nbla10545 Nbla00271 RTN3 RTN1 RTN2

RTN4 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 2 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
VAR_035904⁴		A colorectal cancer sample⁴	--	see VAR_035904	2	L V	mis⁴		0	--	--	--	--
rs150500955^1,2	C	--	55065245(+)	`CATGTC/TTGCCT`	5	--	ds500¹		0	--	--	--	--
rs77408068^1,2	C,F	--	55065324(+)	`CGATTA/GATGAT`	5	--	ds500¹		1		WA	118
rs78708827^1,2	C,F	--	55065441(+)	`CTGCAC/GTGTAT`	5	--	ds500¹		1		NA	120
rs887^1,2	C,F,O,A,H	--	55065457(-)	`TTAACT/CCACAT`	5	--	ds500¹		35		MN EA NA NS WA CSA	5199
rs80098385^1,2	C,F	--	55065479(+)	`ATGAAT/ATTATT`	5	--	ds500¹		1		WA	118
rs191098487^1,2		--	55065501(+)	`AAACAC/TATCAC`	5	--	ds500¹		0	--	--	--	--
rs3839054^1,2	C	--	55065560(-)	`AACAA-/AAGTCAA`	5	--	ds500¹		0	--	--	--	--
rs183285861^1,2		--	55065573(+)	`CCACAA/GTAAAC`	5	--	ds500¹		0	--	--	--	--
rs138875610^1,2	C	--	55065575(+)	`ACAGT-/AAAC AAACA`	5	--	ds500¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for RTN4 (55199325 - 55339757 bp)

Structural Variations
Database of Genomic Variants (DGV) 6 variations for RTN4: About this table

Variant ID	Type	Subtype	PubMed ID
esv2474783	CNV	Deletion	19546169
esv2517082	CNV	Deletion	19546169
esv2720078	CNV	Deletion	23290073
esv267485	CNV	Insertion	20981092
nsv834069	CNV	Loss	17160897
nsv874155	CNV	Loss	21882294

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

RTN4 for disorders           About GeneDecksing

OMIM gene information: 604475    OMIM disorders: --

20/32 diseases for RTN4 (see all 32):    About MalaCards

pathological gambling ventricular septal defect cerebral artery occlusion inclusion body myositis

myositis cerebrovascular accident amyotrophic lateral sclerosis lateral sclerosis

cervical squamous cell carcinoma oligodendroglioma temporal lobe epilepsy adult t-cell leukemia

multiple sclerosis schizophrenia brain disease dilated cardiomyopathy

aortic aneurysm bipolar disorder t-cell leukemia down syndrome

3 diseases from the University of Copenhagen DISEASES database for RTN4:

Amyotrophic lateral sclerosis Multiple sclerosis Cerebrovascular accident

Congresses - knowledge worth sharing:
Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

10/12 Novoseek inferred disease relationships for RTN4 gene (see all 12) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
amyotrophic lateral sclerosis	60.8	15	15786457 (3), 18419791 (2), 12270696 (1), 19889996 (1) (see all 9)
epilepsy temporal lobe	33.9	4	15619232 (1), 15245492 (1), 16772867 (1), 17439704 (1)
neurodegenerative diseases	32.4	1	14644040 (1)
schizophrenia	24.9	28	12425946 (5), 15234466 (4), 17022955 (3), 14741411 (2) (see all 8)
scar	24	3	11597097 (1), 16646157 (1), 15566408 (1)
multiple sclerosis	20.1	7	14644040 (2), 18495952 (2), 20437585 (1), 17356385 (1) (see all 5)
small cell lung cancer	17.9	1	11494121 (1)
tumors	5.29	6	17592524 (2), 12510146 (1), 11891768 (1), 18685489 (1)
cancer	5.21	5	12510146 (2), 11494121 (2), 15781961 (1)
neurological disorders	3.72	2	14644040 (2)

Genetic Association Database (GAD): RTN4
Human Genome Epidemiology (HuGE) Navigator: RTN4 (10 documents)

Export disorders for RTN4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for RTN4 gene, integrated from 9 sources (see all 218):
(articles sorted by number of sources associating them with RTN4)

Utopia: connect your pdf to the dynamic
world of online information

Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. (PubMed id 10667797)^{1, 2, 3, 9} GrandPre T.... Strittmatter S.M. (2000)
Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping. (PubMed id 10773680)^{1, 2, 3} Yang J.... Zhao S.-Y. (2000)
Genomic structure and functional characterisation of the promoters of human and mouse nogo/rtn4. (PubMed id 12488097)^{1, 2, 9} Oertle T.... Schwab M.E. (2003)
No association between the genetic polymorphisms within RTN4 and schizophrenia in the Chinese population. (PubMed id 15234466)^{1, 4, 9} Chen W....He L. (2004)
Nogo CAA 3'UTR Insertion polymorphism is not associated with Schizophrenia nor with bipolar disorder. (PubMed id 15820318)^{1, 4, 9} Gregorio S.P....Dias-Neto E. (2005)
Nogos and the Nogo-66 receptor: factors inhibiting CNS neuron regeneration. (PubMed id 11891768)^{1, 2, 9} Ng C.E.L. and Tang B.L. (2002)
Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells. (PubMed id 16835300)^{1, 2, 9} Miao R.Q.... Sessa W.C. (2006)
CAA insertion polymorphism in the 3'UTR of Nogo gene on 2p14 is not associated with schizophrenia. (PubMed id 15661375)^{1, 4, 9} Xiong L....Joober R. (2005)
Nogo 3'-untranslated region CAA insertion: failure to replicate association with schizophrenia and demonstration of marked population difference in frequency of the insertion. (PubMed id 14741411)^{1, 4, 9} Covault J....Kranzler H. (2004)
The association between dilated cardiomyopathy and RTN4 3'UTR insertion/deletion polymorphisms. (PubMed id 18948092)^{1, 4, 9} Zhou B....Zhang L. (2009)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 57142	HGNC: 14085	AceView: RTN4	Ensembl:ENSG00000115310	euGenes: HUgn57142
ECgene: RTN4	H-InvDB: RTN4

(According to HUGE)
About This Section

HUGE: KIAA0886

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for RTN4	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for RTN4	Genetics and Cytogenetics in Oncology and Haematology
SHMPD	http://shmpd.bii.a-star.edu.sg/gene.php?genestart=R&genename=RTN4+%40+NOGO
Protein Spotlight	http://web.expasy.org/spotlight/back_issues/sptlt069.shtml

Intellectual Property for RTN4 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for RTN4 gene:
Search GeneIP for patents involving RTN4

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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Reticulon 4

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RTN4 (Gene Symbol)
Reticulon 4
NOGO
Neurite Outgrowth Inhibitor
Neuroendocrine-Specific Protein C Homolog
NSP
ASY
NI220/250
NOGO-A
NOGOC
NSP-CL
Nbla00271
Nbla10545
Nogo-B
Nogo-C
RTN-X
RTN4-A
RTN4-B1
RTN4-B2
RTN4-C
foocen
Human NogoA
My043 Protein
Neurite Growth Inhibitor 220
Reticulon 5
reticulon-4
Foocen
KIAA0886
RTN-x
Reticulon-5
Neuroendocrine-Specific Protein
Nogo Protein

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RTN4 Gene

Reticulon 4

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