RTN3

Chr 11

reticulon 3

Also known as: ASYIP, HAP, NSPL2, NSPLII, RTN3-A1

NCBI Gene: 10313ENSG00000133318UniProt: O95197

This gene belongs to the reticulon family of highly conserved genes that are preferentially expressed in neuroendocrine tissues. This family of proteins interact with, and modulate the activity of beta-amyloid converting enzyme 1 (BACE1), and the production of amyloid-beta. An increase in the expression of any reticulon protein substantially reduces the production of amyloid-beta, suggesting that reticulon proteins are negative modulators of BACE1 in cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, and pseudogenes of this gene are located on chromosomes 4 and 12. [provided by RefSeq, May 2012]

171
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RTN3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 148 VUS of 171 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.62LOEUF
pLI 0.000
Z-score 3.24
OE 0.39 (0.25–0.62)
Tolerant

Typical tolerance to LoF variation

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.
-0.24Z-score
OE missense 1.03 (0.96–1.10)
546 obs / 530.5 exp
Tolerant

Tolerant to missense variation

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.0.39 (0.25–0.62)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.96–1.10)
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.1.01
0≤1.21.6
LoF obs/exp: 13 / 33.1Missense obs/exp: 546 / 530.5Syn Z: -0.09

ClinVar Variant Classifications

171 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic3
VUS148
Likely Benign12
Benign3
5
Pathogenic
3
Likely Pathogenic
148
VUS
12
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
3
0
3
VUS
0
147
1
0
148
Likely Benign
0
11
0
1
12
Benign
0
1
0
2
3
Total015993171

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

View in ClinVar →

Protein Context — Lollipop Plot

RTN3 · 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
RETICULON 3; RTN3
MIM #604249 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Effects of altered RTN3 expression on BACE1 activity and Alzheimer's neuritic plaques.
Sharoar MG et al.·Rev Neurosci
2017Review
Targeted proteomics addresses selectivity and complexity of protein degradation by autophagy.
Leytens A et al.·Autophagy
2025
RTN3 regulates collagen biosynthesis and profibrotic macrophage differentiation to promote pulmonary fibrosis via interacting with CRTH2.
Wang CY et al.·Mol Med
2025
Reticulon 3 deficiency induces ferroptosis via chaperone-mediated autophagy in ischemia-reperfusion induced acute kidney injury.
Zhang Y et al.·Free Radic Biol Med
2026
A hypoxia-glycolysis-lactate-related gene signature for prognosis prediction in hepatocellular carcinoma.
Qin X et al.·BMC Med Genomics
2024
Identification of rare RTN3 variants in Alzheimer's disease in Han Chinese.
Zou Y et al.·Hum Genet
2018
The potential role of RTN3 in monocyte recruitment and atherosclerosis.
Chen Y et al.·Mol Cell Biochem
2012
Reticulons promote formation of ER-derived double-membrane vesicles that facilitate SARS-CoV-2 replication.
Williams JM et al.·J Cell Biol
2023
Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer's disease.
Sharoar MG et al.·Mol Psychiatry
2016Functional
Reticulon 3-mediated Chk2/p53 activation suppresses hepatocellular carcinogenesis and is blocked by hepatitis B virus.
Song S et al.·Gut
2021
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