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RTN4RL1

gene
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Also known as NGRH2NgR3DKFZp547J144

Summary

RTN4RL1 (reticulon 4 receptor like 1, HGNC:21329) is a protein-coding gene on chromosome 17p13.3, encoding Reticulon-4 receptor-like 1 (Q86UN2). Cell surface receptor.

Enables signaling receptor activity. Predicted to be involved in negative regulation of axon regeneration. Located in cell surface and plasma membrane.

Source: NCBI Gene 146760 — RefSeq curated summary.

At a glance

  • GWAS associations: 11
  • Clinical variants (ClinVar): 36 total
  • MANE Select transcript: NM_178568

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:21329
Approved symbolRTN4RL1
Namereticulon 4 receptor like 1
Location17p13.3
Locus typegene with protein product
StatusApproved
AliasesNGRH2, NgR3, DKFZp547J144
Ensembl geneENSG00000185924
Ensembl biotypeprotein_coding
OMIM610461
Entrez146760

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000331238

RefSeq mRNA: 1 — MANE Select: NM_178568 NM_178568

CCDS: CCDS45569

Canonical transcript exons

ENST00000331238 — 2 exons

ExonStartEnd
ENSE0000129831019346771937808
ENSE0000176363620248532025334

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 87.96.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2978 / max 71.6969, expressed in 675 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
1637911.3457517
1637890.8066394
1637900.6752349
1637920.2541163
1637880.2162110

Top tissues by expression

246 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
cortical plateUBERON:000534387.96gold quality
middle temporal gyrusUBERON:000277183.49gold quality
prefrontal cortexUBERON:000045182.37gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099181.45gold quality
frontal cortexUBERON:000187080.75gold quality
right frontal lobeUBERON:000281080.38gold quality
dorsolateral prefrontal cortexUBERON:000983479.65gold quality
neocortexUBERON:000195079.56gold quality
Brodmann (1909) area 9UBERON:001354079.05gold quality
cerebral cortexUBERON:000095678.15gold quality
superior frontal gyrusUBERON:000266177.77gold quality
anterior cingulate cortexUBERON:000983576.99gold quality
skin of abdomenUBERON:000141676.86gold quality
endothelial cellCL:000011576.58silver quality
primary visual cortexUBERON:000243676.52gold quality
skin of legUBERON:000151175.37gold quality
postcentral gyrusUBERON:000258175.32gold quality
parietal lobeUBERON:000187274.90gold quality
Ammon’s hornUBERON:000195474.44gold quality
entorhinal cortexUBERON:000272874.41gold quality
zone of skinUBERON:000001474.35gold quality
occipital lobeUBERON:000202174.02gold quality
Brodmann (1909) area 23UBERON:001355473.59gold quality
temporal lobeUBERON:000187172.35gold quality
forebrainUBERON:000189072.33gold quality
upper arm skinUBERON:000426372.29gold quality
amygdalaUBERON:000187670.90gold quality
brainUBERON:000095570.87gold quality
adenohypophysisUBERON:000219670.86gold quality
pituitary glandUBERON:000000770.60gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-MTAB-6075no5.38
E-ANND-3no1.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

146 targeting RTN4RL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-190A-3P100.0080.355520
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-9-5P100.0072.282361
HSA-MIR-6873-3P100.0071.422626
HSA-MIR-6833-3P100.0070.633197
HSA-MIR-4768-5P100.0069.492861
HSA-MIR-340-5P100.0072.504437
HSA-MIR-126-5P100.0072.713180
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-7110-3P100.0073.182486
HSA-MIR-574-5P100.0066.01989
HSA-MIR-3163100.0077.238605
HSA-MIR-34A-5P99.9971.211784
HSA-MIR-449A99.9971.051776
HSA-MIR-6870-5P99.9968.552115
HSA-MIR-19A-3P99.9875.332762
HSA-MIR-19B-3P99.9875.442754
HSA-MIR-34C-5P99.9770.451577
HSA-MIR-449B-5P99.9770.261580
HSA-MIR-4723-5P99.9768.702034
HSA-MIR-569899.9768.492029
HSA-MIR-7111-5P99.9768.482062
HSA-MIR-512-3P99.9767.351049
HSA-MIR-314899.9775.066478
HSA-MIR-548AJ-3P99.9673.385345
HSA-MIR-548X-3P99.9673.385345
HSA-MIR-185-3P99.9567.011743
HSA-MIR-3912-5P99.9566.11925
HSA-MIR-141-3P99.9472.792421

Literature-anchored findings (GeneRIF, showing 4)

  • predominantly expressed in the neurons of the embryonic and adult nervous systems (PMID:14664809)
  • Nogo receptor 3, a paralog of NgR1,functions as a NgR1 co-receptor for Nogo-66. (PMID:22133682)
  • Duplication of 10q22.3-q23.3 encompassing NGR3 gene is associated with congenital heart disease, microcephaly, and mild intellectual disability (PMID:26383923)
  • RTN4RL1 plays an important role in promoting the EMT of nasopharyngeal carcinoma (NPC) by regulating the phosphorylation of Src and FAK, thus activating their downstream pathways and eventually altering E-cadherin levels, F-actin polymerization, and cell polarity. Additionally, a high level of RTN4RL1 correlates with a poor prognosis of NPC. (PMID:29327067)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriortn4rl1aENSDARG00000007856
danio_reriortn4rl1bENSDARG00000098528
mus_musculusRtn4rl1ENSMUSG00000045287
rattus_norvegicusRtn4rl1ENSRNOG00000003121

Paralogs (22): DCN (ENSG00000011465), RTN4R (ENSG00000040608), ASPN (ENSG00000106819), FLRT3 (ENSG00000125848), FLRT1 (ENSG00000126500), LRRC4 (ENSG00000128594), LRRC4B (ENSG00000131409), PODNL1 (ENSG00000132000), LRTM1 (ENSG00000144771), LRRC4C (ENSG00000148948), LRRTM1 (ENSG00000162951), LRRC15 (ENSG00000172061), PODN (ENSG00000174348), LRRTM4 (ENSG00000176204), BGN (ENSG00000182492), LRRC19 (ENSG00000184434), FLRT2 (ENSG00000185070), GP1BA (ENSG00000185245), RTN4RL2 (ENSG00000186907), NYX (ENSG00000188937), LRRC66 (ENSG00000188993), LRRTM3 (ENSG00000198739)

Protein

Protein identifiers

Reticulon-4 receptor-like 1 — Q86UN2 (reviewed: Q86UN2)

Alternative names: Nogo receptor-like 2, Nogo-66 receptor homolog 2, Nogo-66 receptor-related protein 3

All UniProt accessions (1): Q86UN2

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface receptor. Plays a functionally redundant role in postnatal brain development and in regulating axon regeneration in the adult central nervous system. Contributes to normal axon migration across the brain midline and normal formation of the corpus callosum. Protects motoneurons against apoptosis; protection against apoptosis is probably mediated by MAG. Plays a role in inhibiting neurite outgrowth and axon regeneration via its binding to neuronal chondroitin sulfate proteoglycans. Binds heparin. Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development. Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton.

Subunit / interactions. Identified in a complex that contains RTN4R, RTN4RL1 and NGFR; the interaction depends on the presence of chondroitin sulfate proteoglycans. Does not interact with MAG, OMG and RTN4.

Subcellular location. Cell membrane. Membrane raft. Perikaryon. Cell projection.

Tissue specificity. Predominantly expressed in brain. Expressed at lower levels in kidney, lung, mammary gland, placenta, salivary gland, skeletal muscle and spleen.

Similarity. Belongs to the Nogo receptor family.

RefSeq proteins (1): NP_848663* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000483Cys-rich_flank_reg_CDomain
IPR001611Leu-rich_rptRepeat
IPR003591Leu-rich_rpt_typical-subtypRepeat
IPR032675LRR_dom_sfHomologous_superfamily
IPR050541LRR_TM_domain-containingFamily

Pfam: PF13855

UniProt features (20 total): repeat 8, compositionally biased region 3, domain 2, region of interest 2, signal peptide 1, chain 1, lipid moiety-binding region 1, sequence conflict 1, propeptide 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q86UN2-F176.780.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 420

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-163125Post-translational modification: synthesis of GPI-anchored proteins

MSigDB gene sets: 184 (showing top): GGGACCA_MIR133A_MIR133B, TAATAAT_MIR126, GOBP_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOCC_CELL_SURFACE, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, RACCACAR_AML_Q6, GOBP_RESPONSE_TO_AXON_INJURY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, LHX3_01, CHX10_01, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (5): negative regulation of neuron projection development (GO:0010977), corpus callosum development (GO:0022038), axon regeneration (GO:0031103), negative regulation of axon regeneration (GO:0048681), positive regulation of synapse assembly (GO:0051965)

GO Molecular Function (4): heparin binding (GO:0008201), chondroitin sulfate binding (GO:0035374), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), plasma membrane (GO:0005886), cell surface (GO:0009986), cell projection (GO:0042995), perikaryon (GO:0043204), membrane raft (GO:0045121), extracellular exosome (GO:0070062), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Post-translational protein modification1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure6
glycosaminoglycan binding2
sulfur compound binding2
membrane2
regulation of neuron projection development1
neuron projection development1
negative regulation of cell projection organization1
telencephalon development1
anatomical structure development1
neuron projection regeneration1
response to axon injury1
axon development1
axon regeneration1
negative regulation of response to external stimulus1
regulation of axon regeneration1
negative regulation of neuron projection regeneration1
negative regulation of response to wounding1
synapse assembly1
positive regulation of nervous system development1
regulation of synapse assembly1
positive regulation of cell junction assembly1
molecular transducer activity1
binding1
cell periphery1
neuronal cell body1
membrane microdomain1
extracellular vesicle1
leaflet of membrane bilayer1

Protein interactions and networks

STRING

928 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
RTN4RL1RTN4Q9NQC3950
RTN4RL1PTPRSQ13332812
RTN4RL1MAGP20916739
RTN4RL1OMGP23515692
RTN4RL1PTPRFP10586622
RTN4RL1S1PR2O95136487
RTN4RL1SMYD4Q8IYR2474
RTN4RL1PLAAT1Q9HDD0455
RTN4RL1ERBB4Q15303438
RTN4RL1TNFRSF19Q9NS68434
RTN4RL1BCANQ96GW7426
RTN4RL1EPHA10Q5JZY3425
RTN4RL1SLC6A17Q9H1V8422
RTN4RL1SLC2A1P11166421
RTN4RL1ST3GAL5Q9UNP4420

IntAct

19 interactions, top by confidence:

ABTypeScore
RTN4RL1KRTAP10-7psi-mi:“MI:0915”(physical association)0.560
RTN4RL1KRTAP10-8psi-mi:“MI:0915”(physical association)0.560
RTN4RL1NOTCH2NLApsi-mi:“MI:0915”(physical association)0.560
RTN4RL1psi-mi:“MI:0915”(physical association)0.560
RTN4RL1psi-mi:“MI:0915”(physical association)0.560
KRTAP10-8RTN4RL1psi-mi:“MI:0915”(physical association)0.560
NOTCH2NLARTN4RL1psi-mi:“MI:0915”(physical association)0.560
NOTCH2NLCRTN4RL1psi-mi:“MI:0915”(physical association)0.560
KRTAP1-1RTN4RL1psi-mi:“MI:0915”(physical association)0.560
RTN4RL1NOTCH2NLCpsi-mi:“MI:0915”(physical association)0.000
KRTAP1-1RTN4RL1psi-mi:“MI:0915”(physical association)0.000
RTN4RL1KRTAP1-1psi-mi:“MI:0915”(physical association)0.000

BioGRID (13): KRTAP10-7 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), RTN4RL1 (Affinity Capture-RNA), RTN4RL1 (Affinity Capture-RNA), KRTAP1-1 (Two-hybrid), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid), RTN4RL1 (Affinity Capture-RNA), RTN4RL1 (Affinity Capture-RNA), RTN4RL1 (Two-hybrid), RTN4RL1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4H9, A2ARI4, A6NDA9, B0BLW3, B4F7C5, D3ZAL8, D3ZTV3, D4A6D8, D4A7P2, E7FE13, F1MT22, O14498, O43155, O43300, P0DM44, P83286, Q149C3, Q5NVQ6, Q5R6B1, Q5R7M3, Q5RAC4, Q6PFC5, Q6RKD8, Q80WD0, Q80XG9, Q80ZD7, Q80ZD8, Q80ZD9, Q810C0, Q810C1, Q86SJ2, Q86UE6, Q86UN2, Q86VH4, Q86VH5, Q86WK6, Q8BGA3, Q8BLU0, Q8BZ81, Q8C2S7

Diamond homologs: A0N0X6, A1KZ92, A2A8L5, A3KNN3, A4IFW2, A4IGL7, A4IIW9, A6H793, A7MBJ4, A8WGA3, B0BNK7, B0V2N1, B3MH43, B3NS99, B4GBH0, B4HNW4, B4KPU0, B4MR28, B4P5Q9, B4QC63, D2HFT7, D3YXG0, D4A1J9, D4ABX8, E9Q7T7, F1MLX5, F1NWE3, F1NY98, O55005, O60469, O75325, O89026, O94779, O95428, P0C6S8, P0C7J6, P10586, P16621, P59034, P59035

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

36 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance29
Likely benign2
Benign4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1257 predictions. Top by Δscore:

VariantEffectΔscore
17:1937805:CACC:Cacceptor_gain0.9900
17:1937807:CC:Cacceptor_gain0.9900
17:1937808:CC:Cacceptor_gain0.9900
17:1937809:C:CCacceptor_gain0.9900
17:1937813:C:CTacceptor_gain0.9900
17:1945728:T:Adonor_gain0.9900
17:2024848:CTCA:Cdonor_loss0.9900
17:2024849:TCAC:Tdonor_loss0.9900
17:2024850:CACCT:Cdonor_loss0.9900
17:2024852:C:CGdonor_loss0.9900
17:1937806:ACCCT:Aacceptor_loss0.9800
17:1937807:CCCT:Cacceptor_loss0.9800
17:1937808:CCTGG:Cacceptor_loss0.9800
17:1937809:C:Tacceptor_gain0.9800
17:1937809:CTG:Cacceptor_loss0.9800
17:1937810:T:Aacceptor_loss0.9800
17:1937814:A:Tacceptor_gain0.9800
17:1949832:T:Cdonor_gain0.9800
17:2024851:A:ACdonor_gain0.9800
17:2024852:C:CCdonor_gain0.9800
17:1937806:ACC:Aacceptor_gain0.9700
17:1937807:CCC:Cacceptor_gain0.9700
17:1964197:T:Cacceptor_gain0.9700
17:1998562:T:Adonor_gain0.9500
17:2023758:CGACA:Cdonor_gain0.9500
17:2024758:C:Adonor_gain0.9500
17:2023723:C:Adonor_gain0.9400
17:2023728:T:TAdonor_gain0.9400
17:1937804:GCACC:Gacceptor_gain0.9300
17:1937805:CACCC:Cacceptor_gain0.9300

AlphaMissense

2872 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:1937217:A:GL202P1.000
17:1937289:A:GL178P1.000
17:1937345:G:CN159K1.000
17:1937345:G:TN159K1.000
17:1937355:A:GL156P1.000
17:1937361:A:GL154P1.000
17:1937433:A:GL130P1.000
17:1937433:A:TL130H1.000
17:1937442:A:TL127H1.000
17:1937492:G:CN110K1.000
17:1937492:G:TN110K1.000
17:1937508:A:GL105P1.000
17:1937564:G:CN86K1.000
17:1937564:G:TN86K1.000
17:1937565:T:AN86I1.000
17:1937566:T:AN86Y1.000
17:1937580:A:GL81P1.000
17:1937630:G:CN64K1.000
17:1937630:G:TN64K1.000
17:1937631:T:AN64I1.000
17:1937640:A:GL61P1.000
17:1937642:G:CF60L1.000
17:1937642:G:TF60L1.000
17:1937643:A:CF60C1.000
17:1937643:A:GF60S1.000
17:1937644:A:GF60L1.000
17:1937702:G:CC40W1.000
17:1937703:C:GC40S1.000
17:1937703:C:TC40Y1.000
17:1937704:A:GC40R1.000

dbSNP variants (sampled 300 via entrez): RS1000005285 (17:1963981 C>T), RS1000014584 (17:1999495 T>C), RS1000063410 (17:2000038 A>G), RS1000071616 (17:1960071 G>C,T), RS1000123009 (17:2003490 G>A,C), RS1000146293 (17:1993402 T>C), RS1000153752 (17:1935644 G>GTATAGTT), RS1000161461 (17:1968610 C>T), RS1000171985 (17:1936311 G>A), RS1000175661 (17:2003715 T>A), RS1000252860 (17:2009216 T>C), RS1000265502 (17:1967022 G>A), RS1000265523 (17:1963827 G>A,T), RS1000314019 (17:1944003 G>C), RS1000373908 (17:1962066 G>C)

Disease associations

OMIM: gene MIM:610461 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

StudyTraitp-value
GCST002875_126Diisocyanate-induced asthma1.000000e-06
GCST004029_38Angiotensin-converting enzyme inhibitor intolerance6.000000e-06
GCST004781_8Sulfasalazine-induced agranulocytosis1.000000e-07
GCST005912_1Type 2 diabetes3.000000e-07
GCST008103_174Bipolar disorder8.000000e-06
GCST009701_6Body mass index5.000000e-06
GCST010703_278Brain morphology (MOSTest)2.000000e-15
GCST010988_54Adult body size1.000000e-17
GCST011122_8Walking pace2.000000e-09
GCST011983_18Fasting glucose2.000000e-06
GCST012465_12Bipolar disorder3.000000e-08

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0006995response to diisocyanate
EFO:0005325response to angiotensin-converting enzyme inhibitor
EFO:0004340body mass index
EFO:0004346neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidincreases methylation, affects cotreatment, increases expression, decreases expression, affects expression6
sodium arseniteaffects expression, decreases expression2
Silicon Dioxidedecreases expression, increases expression2
propionaldehydeincreases expression1
trichostatin Adecreases expression1
cinnamaldehydedecreases expression1
butyraldehydeincreases expression1
benzo(e)pyreneincreases methylation1
S-(1,2-dichlorovinyl)cysteineaffects response to substance, increases expression, affects cotreatment, decreases expression1
pentanalincreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression1
nutlin 3increases expression1
dorsomorphinaffects cotreatment, decreases expression1
jinfukangaffects cotreatment, increases expression1
Sunitinibdecreases expression1
Fulvestrantincreases methylation1
Air Pollutantsdecreases expression, increases abundance1
Aldehydesincreases expression1
Benzo(a)pyreneincreases methylation1
Cisplatinincreases expression, affects cotreatment1
Dexamethasoneaffects cotreatment, increases expression1
Diethylhexyl Phthalatedecreases expression1
Doxorubicindecreases expression1
Estradioldecreases expression, affects cotreatment1
Hydralazineaffects cotreatment, increases expression1
Indomethacinaffects cotreatment, increases expression1
Leadaffects expression1
Lipopolysaccharidesaffects response to substance, increases expression, affects cotreatment, decreases expression1
Methapyrileneincreases methylation1
Niclosamideincreases expression1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 75

This page pulls from 75 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot