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RTN4 Gene

protein-coding GIFtS: 68
GCID: GC02M055199

Reticulon 4

See RTN4-related disease
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)
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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, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 schizophrenia. 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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000002.11 NT_022184.16 NC_018913.2

Regulatory elements:

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 Chromatin IP Primers for RTN4

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing 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 ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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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

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:

Ubiquitination² at Lys1090, Lys1104, Lys1171

Modification sites at PhosphoSitePlus

See RTN4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

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

RTN4 Human Recombinant Protein Products:

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	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
	Search eBioscience for Proteins for RTN4
	antibodies-online proteins for RTN4 (7 products)
	antibodies-online peptides for RTN4

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
	Novus Biologicals RTN4 Antibodies
	Abcam antibodies for RTN4
	Cloud-Clone Corp. Antibodies for RTN4
	ThermoFisher Antibodies for RTN4
	antibodies-online antibodies for RTN4 (115 products)

RTN4 Assay Products:

	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
	Search eBioscience for ELISAs for RTN4
	antibodies-online kits for RTN4 (12 products)

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

Find genes that share domains with RTN4 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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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): 2 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005515	protein binding	IPI	11126360
GO:0044822	poly(A) RNA binding	IDA	--

Find genes that share ontologies with RTN4 About GenesLikeMe

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

cellular

mortality/aging

nervous system

normal

Find genes that share phenotypes with RTN4 About GenesLikeMe

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

genOway: Develop your customized and physiologically relevant rodent model for RTN4

miRNA Products:		miRTarBase miRNAs that target RTN4: hsa-mir-320a (MIRT044751), hsa-mir-30c-5p (MIRT047850), hsa-mir-132-3p (MIRT021845), hsa-mir-21-5p (MIRT000167), hsa-mir-183-5p (MIRT024991), hsa-mir-148b-3p (MIRT019491), hsa-mir-33a-5p (MIRT028224), hsa-mir-16-5p (MIRT001421), hsa-mir-34a-5p (MIRT025475), hsa-mir-101-3p (MIRT027341)

		Block miRNA regulation of human, mouse, rat RTN4 using miScript Target Protectors
		Selected qRT-PCR 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:		OriGene RNAi products in human, mouse, rat for RTN4
		Predesigned siRNA for gene silencing in human, mouse, rat RTN4

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for RTN4

Clone Products:		OriGene clones in human, mouse for RTN4 (see all 35) 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
		Browse ESI BIO Cell Lines and PureStem Progenitors for RTN4

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for RTN4

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

RTN4_HUMAN, Q9NQC3: Endoplasmic reticulum membrane; Multi-pass membrane protein. Note=Anchored to the membrane

of the endoplasmic reticulum through 2 putative transmembrane domains

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
endoplasmic reticulum	5
nucleus	5
plasma membrane	4
cytoskeleton	2
cytosol	1

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Gene Ontology (GO): Selected cellular component terms (see all 7): 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:0016021	integral component of membrane	--	--
GO:0030176	integral component of endoplasmic reticulum membrane	IDA	10667797

Find genes that share ontologies with RTN4 About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to 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 QIAGEN, 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 Apr 2014 via Entrez Gene).
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SuperPaths for RTN4 About (see all 7)

See pathways by source

Powered
by

SuperPath

Contained pathways About

p75 NTR receptor-mediated signalling

	p75 NTR receptor-mediated signalling	0.74			p75NTR regulates axonogenesis	0.00
	Axonal growth inhibition (RHOA activation)	0.00

Signaling by FGFR

Signalling by NGF

0.71

Signaling by GPCR

Signal Transduction

0.58

Cell adhesion Integrin-mediated cell adhesion and migration

Development MAG-dependent inhibition of neurite outgrowth

0.42

Spinal Cord Injury

Spinal Cord Injury

Find genes that share SuperPaths with RTN4 About GenesLikeMe

Pathways by source See SuperPaths
Show all pathways

1 Downloadable PowerPoint Slide of GeneGlobe 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

1 Reactome Pathway for RTN4

Axonal growth inhibition (RHOA activation)

Pathway & Disease-focused RT² Profiler PCR Arrays including RTN4:

Neurogenesis in human mouse rat

Nephrotoxicity in human mouse rat

Apoptosis 384HT in human mouse rat

Interactions:

GeneGlobe Interaction Network for RTN4

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

Selected Interacting proteins for RTN4 (Q9NQC3^{1, 2, 3} ENSP00000337838⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 123)

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

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Gene Ontology (GO): Selected biological process terms (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	--

Find genes that share ontologies with RTN4 About GenesLikeMe

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

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)

Find genes that share compounds with RTN4 About GenesLikeMe

(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,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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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:		Block miRNA regulation of human, mouse, rat RTN4 using miScript Target Protectors
		Selected qRT-PCR 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:		OriGene RNAi products in human, mouse, rat for RTN4
		Predesigned siRNA for gene silencing in human, mouse, rat RTN4

Clone Products:		OriGene clones in human, mouse for RTN4 (see all 35) 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
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat RTN4
		QuantiTect SYBR Green Assays in human, mouse, rat RTN4
		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

Selected 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

Selected AceView cDNA sequences (see all 1507):

BM666337 AU104978 BU684302 AI217084 CB108617 AW673265 AA058672 CN483287

CB133824 AA370615 CD723962 AK130812 CB148622 AU104981 BM709363 T34690

R96423 AA331600 AI828700 AA307342 BE302112 BU952509 BX439214 N73666

GeneLoc Exon Structure

Selected 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™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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RTN4 expression in normal human tissues (normalized intensities)
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
selected tissues (see all 20) fully expand


Brain (Nervous System) fully expand to see all 4 entries
Myelinating Oligodendrocyte Cells Forebrain White Matter
Cerebellum

Eye (Sensory Organs)
Retina

Bone (Muscoskeletal System)
Bone Marrow

Colon (Gastrointestinal Tract)

Uterus (Reproductive System)

RTN4 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

RTN4 Protein Expression

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

Pathway & Disease-focused RT² Profiler PCR Arrays including RTN4:

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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)
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This gene was present in the common ancestor of animals.

Orthologs for RTN4 gene from Selected species (see all 17) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Rtn4^{1 , 5}	reticulon 4^{1, 5}	83.56(n)¹ 77.72(a)¹		11 (16.79 cM)⁵ 68585¹ NM_194054.3¹ NP_918943.1¹ 29692947⁵
chicken (Gallus gallus)	Aves	LOC101749579¹	reticulon-4-like	60.49(n) 44.32(a)		101749579 XM_004940171.1 XP_004940228.1
lizard (Anolis carolinensis)	Reptilia	RTN4⁶	reticulon 4	45(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
fruit fly (Drosophila melanogaster)	Insecta	Rtnl1⁶ Rtnl2⁶ (see all 3)	Rtnl2 (see all 3)	27(a) 22(a) (see all 3)	many ↔ many many ↔ many (see all 3)	2L(4992808-5009720) 3R(3354586-3355963)
worm (Caenorhabditis elegans)	Secernentea	ret-1⁶	Protein RET-1, isoform c	7(a)	1 → many	V(14829177-14847312) WBGene00004336

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)
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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

Find genes that share paralogs with RTN4 About GenesLikeMe

(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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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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

Site Specific Mutation Identification with PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 604475 OMIM disorders: --

1 disease for RTN4:
About MalaCards

schizophrenia

3 inferred disease relationships from the University of Copenhagen DISEASES database for RTN4:

Amyotrophic lateral sclerosis Multiple sclerosis Cerebrovascular accident

Find genes that share disorders with RTN4 About GenesLikeMe

Selected 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)
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PubMed articles for RTN4 gene, integrated from 10 sources (see all 223):
(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. (Nature 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. (Cytogenet. Cell Genet. 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. (J. Mol. Biol. 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. (Neurosci. Lett. 2004)
Nogo CAA 3'UTR Insertion polymorphism is not associated with Schizophrenia nor with bipolar disorder. (PubMed id 15820318)^{1, 4, 9} GregA^rio S.P....Dias-Neto E. (Schizophr. Res. 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. (J. Neurosci. Res. 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. (Proc. Natl. Acad. Sci. U.S.A. 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. (Brain Res. Mol. Brain Res. 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. (Brain Res. Mol. Brain Res. 2004)
The association between dilated cardiomyopathy and RTN4 3'UTR insertion/deletion polymorphisms. (PubMed id 18948092)^{1, 4, 9} Zhou B....Zhang L. ( international journal of clinical chemistry 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)
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Entrez Gene: 57142	HGNC: 14085	AceView: RTN4	Ensembl:ENSG00000115310	euGenes: HUgn57142
ECgene: RTN4	H-InvDB: RTN4

(According to HUGE)
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HUGE: KIAA0886

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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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/069

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

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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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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