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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LTN1
listerin E3 ubiquitin protein ligase 1
Chromosome 21 · 21q21.3
NCBI Gene: 26046Ensembl: ENSG00000198862.15HGNC: HGNC:13082UniProt: O94822
94PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
rescue of stalled cytosolic ribosomecytosolcytosolic ribosomeRQC complexAlzheimer diseaseovarian neoplasmNeurodevelopmental disorderhepatocellular carcinoma
✦AI Summary

LTN1 (listerin E3 ubiquitin protein ligase 1) is a core E3 ubiquitin ligase component of the ribosome-associated quality control (RQC) complex, a surveillance mechanism that eliminates incomplete nascent polypeptides produced during translation stalling 1. Within RQC, LTN1 is recruited to obstructed ribosomal subunits by NEMF and mediates ubiquitination of stalled nascent chains 2. This ubiquitination targets substrates for VCP/p97-dependent extraction and proteasomal degradation 1. Beyond canonical cytoplasmic RQC, LTN1 operates at the endoplasmic reticulum and mitochondria 1. Recently, LTN1 has been shown to suppress RAN (repeat-associated non-AUG) translation from GC-rich repeats, with depletion markedly increasing toxic RAN products from C9ORF72 and FMR1 repeats implicated in neurodegeneration 3. Additionally, LTN1 recruits TRIM27 to ubiquitinate RIG-I-like receptors for ESCRT-dependent degradation, negatively regulating antiviral innate immunity 4. LTN1 mutations cause neurodegeneration in mice, and RQC defects impair cellular fitness 12, highlighting LTN1's critical role in protein quality control and disease prevention.

Sources cited
1
LTN1/Listerin E3 ligase is stabilized by NEMF to bind obstructed ribosomal subunits for nascent-chain ubiquitylation; RQC defects cause neurodegeneration
PMID: 35452614
2
LTN1/listerin is an E3 ubiquitin ligase that targets aberrant nascent polypeptides for proteasomal degradation; mutations cause neurodegeneration; RQC operates on ER and mitochondria surfaces
PMID: 30940912
3
LTN1 depletion markedly boosts RAN translation from GC-rich repeats (G4C2 and CGG); RQC factor augmentation is proposed as therapeutic strategy for repeat expansion disorders
PMID: 38412259
4
LTN1 recruits TRIM27 to trigger K63-linked polyubiquitination of RIG-I and MDA5, facilitating ESCRT-dependent degradation to negatively regulate antiviral immunity
PMID: 38060409
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.25Weak
ovarian neoplasmOpen Targets
0.25Weak
Neurodevelopmental disorderOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.07Suggestive
atherosclerosisOpen Targets
0.07Suggestive
familial amyotrophic lateral sclerosisOpen Targets
0.06Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
amyotrophic lateral sclerosisOpen Targets
0.05Suggestive
delta-beta-thalassemiaOpen Targets
0.05Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.05Suggestive
dominant beta-thalassemiaOpen Targets
0.05Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.04Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.04Suggestive
Alpha-thalassemia - myelodysplastic syndromeOpen Targets
0.04Suggestive
alpha-thalassemia-myelodysplastic syndromeOpen Targets
0.04Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.04Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
KeloidOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RPL12Protein interaction100%RPL39Protein interaction100%RPL13AProtein interaction100%RPL38Protein interaction100%RPL27Protein interaction100%RPL29Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
50%
Brain
45%
Ovary
36%
Liver
31%
Lung
30%
Gene Interaction Network
Click a node to explore
LTN1RPL12RPL39RPL13ARPL38RPL27RPL29
PROTEIN STRUCTURE
Preparing viewer…
PDB9GY4 · 3.00 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.47Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.37 [0.29–0.47]
RankingsWhere LTN1 stands among ~20K protein-coding genes
  • #5,092of 20,598
    Most Researched94 · top quartile
  • #2,702of 17,882
    Most Constrained (LOEUF)0.47 · top quartile
Genes detectedLTN1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Ribosome-associated quality-control mechanisms from bacteria to humans.
PMID: 35452614
Mol Cell · 2022
1.00
2
Mechanisms and functions of ribosome-associated protein quality control.
PMID: 30940912
Nat Rev Mol Cell Biol · 2019
0.90
3
Argonaute-dependent ribosome-associated protein quality control.
PMID: 35981909
Trends Cell Biol · 2023
0.80
4
Remodeling of the ribosomal quality control and integrated stress response by viral ubiquitin deconjugases.
PMID: 38097648
Nat Commun · 2023
0.70
5
Ribosomal quality control factors inhibit repeat-associated non-AUG translation from GC-rich repeats.
PMID: 38412259
Nucleic Acids Res · 2024
0.60