RTN4R

Chr 22AD

reticulon 4 receptor

Also known as: NGR, NOGOR, NgR1

NCBI Gene: 65078ENSG00000040608UniProt: Q9BZR6

This gene encodes the receptor for reticulon 4, oligodendrocyte myelin glycoprotein and myelin-associated glycoprotein. This receptor mediates axonal growth inhibition and may play a role in regulating axonal regeneration and plasticity in the adult central nervous system. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Schizophrenia, susceptibility to}MIM #181500
AD
482
ClinVar variants
372
Pathogenic / LP
0.96
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RTN4R
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
372 Pathogenic / Likely Pathogenic· 98 VUS of 482 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.30LOEUF
pLI 0.959
Z-score 2.93
OE 0.00 (0.00–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.13Z-score
OE missense 0.82 (0.74–0.91)
265 obs / 322.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.74–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 0 / 10.0Missense obs/exp: 265 / 322.2Syn Z: 0.13

ClinVar Variant Classifications

482 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic363
Likely Pathogenic9
VUS98
Likely Benign10
Benign2
363
Pathogenic
9
Likely Pathogenic
98
VUS
10
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
363
0
363
Likely Pathogenic
0
0
9
0
9
VUS
0
87
11
0
98
Likely Benign
0
3
0
7
10
Benign
0
0
2
0
2
Total0903857482

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RTN4R · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Schizophrenia, susceptibility to}

MIM #181500

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Proteomic signatures for identification of impaired glucose tolerance.
Carrasco-Zanini J et al.·Nat Med
2022
A novel rare variant R292H in RTN4R affects growth cone formation and possibly contributes to schizophrenia susceptibility.
Kimura H et al.·Transl Psychiatry
2017
Exploring potential therapeutic targets for cardiomyopathy: A proteome-wide Mendelian randomization analysis.
Ji Y et al.·Medicine (Baltimore)
2025
Nogo Receptor 1 (RTN4R) as a candidate gene for schizophrenia: analysis using human and mouse genetic approaches.
Hsu R et al.·PLoS One
2007Functional
Genetic and clinical features of social cognition in 22q11.2 deletion syndrome.
Lattanzi GM et al.·J Neurosci Res
2018Review
A common functional allele of the Nogo receptor gene, reticulon 4 receptor (RTN4R), is associated with sporadic amyotrophic lateral sclerosis in a French population.
Amy M et al.·Amyotroph Lateral Scler Frontotemporal Degener
2015Functional
Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia.
Sinibaldi L et al.·Hum Mutat
2004
Development of neural repair therapy for chronic spinal cord trauma: soluble Nogo receptor decoy from discovery to clinical trial.
Howard EM et al.·Curr Opin Neurol
2023Review
Identification of miRNA-mRNA Network Associated with Acute Myeloid Leukemia Survival.
Zhang C et al.·Med Sci Monit
2017
Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG genes in patients with non-syndromic mental retardation.
Venturin M et al.·Neurogenetics
2006Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools