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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TNRC6C
trinucleotide repeat containing adaptor 6C
Chromosome 17 · 17q25.3
NCBI Gene: 57690Ensembl: ENSG00000078687.19HGNC: HGNC:29318UniProt: Q9HCJ0
69PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
miRNA-mediated post-transcriptional gene silencingprotein bindingpositive regulation of nuclear-transcribed mRNA poly(A) tail shorteningpositive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decaycancerAbnormality of the skeletal systemmathematical abilitysmoking initiation
✦AI Summary

TNRC6C functions as a critical scaffolding protein in the microRNA (miRNA)-mediated gene silencing pathway. The protein contains distinct functional domains: an N-terminal GW-repeat region that directly interacts with all four human Argonaute proteins (AGO1-AGO4) 1, and a C-terminal silencing domain that mediates translational repression and mRNA degradation independently of Argonaute binding 12. The C-terminal domain, which includes an RRM RNA-binding motif, serves as a key effector for protein synthesis repression through effects on both mRNA stability and translation 2. TNRC6C can recruit deadenylase complexes to promote mRNA decay 1. Additionally, TNRC6C interacts with GIGYF proteins through proline-rich sequences, bridging 4EHP to Argonaute-miRNA complexes for transcript-specific translational repression 3. Functionally, TNRC6C appears less critical than its paralogs TNRC6A and TNRC6B for siRNA off-target effects and hepatotoxicity 4. The gene has clinical relevance in thyroid cancer, where the antisense lncRNA TNRC6C-AS1 promotes tumor progression by regulating downstream targets through competitive endogenous RNA mechanisms 56.

Sources cited
1
TNRC6C N-terminal domain interacts with AGO1-AGO4 proteins and C-terminal domain mediates silencing independently
PMID: 19383768
2
C-terminal domain containing RRM motif is key for translational repression activity
PMID: 19304925
3
TNRC6C interacts with GIGYF proteins through proline-rich sequences to bridge 4EHP complexes
PMID: 36854607
4
TNRC6C knockdown has minimal impact on siRNA off-target effects compared to TNRC6A/B
PMID: 40134378
5
TNRC6C-AS1 lncRNA promotes thyroid cancer progression through miR-129-5p/UNC5B axis
PMID: 29893424
6
TNRC6C-AS1 promotes thyroid carcinoma through STK4 methylation and Hippo signaling
PMID: 31657132
Disease Associationsⓘ20
cancerOpen Targets
0.46Moderate
Abnormality of the skeletal systemOpen Targets
0.35Weak
mathematical abilityOpen Targets
0.31Weak
smoking initiationOpen Targets
0.30Weak
alcohol drinkingOpen Targets
0.27Weak
complicationOpen Targets
0.25Weak
Herpes ZosterOpen Targets
0.25Weak
nervous system diseaseOpen Targets
0.25Weak
androgenetic alopeciaOpen Targets
0.24Weak
myopathyOpen Targets
0.23Weak
injuryOpen Targets
0.22Weak
hypertensionOpen Targets
0.19Weak
bone fractureOpen Targets
0.19Weak
adolescent idiopathic scoliosisOpen Targets
0.19Weak
esophageal varicesOpen Targets
0.19Weak
corneal dystrophyOpen Targets
0.17Weak
Abruptio PlacentaeOpen Targets
0.17Weak
viral pneumoniaOpen Targets
0.17Weak
obesityOpen Targets
0.17Weak
chronic laryngitisOpen Targets
0.16Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CNOT6LProtein interaction100%AGO3Protein interaction100%PAN2Protein interaction100%AGO1Protein interaction99%CNOT7Protein interaction99%AGO4Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Heart
89%
Ovary
86%
Bone Marrow
49%
Liver
48%
Lung
40%
Gene Interaction Network
Click a node to explore
TNRC6CCNOT6LAGO3PAN2AGO1CNOT7AGO4
PROTEIN STRUCTURE
Preparing viewer…
PDB2X04 · 1.49 Å · X-ray
View on RCSB ↗
RankingsWhere TNRC6C stands among ~20K protein-coding genes
  • #6,858of 20,598
    Most Researched69
Genes detectedTNRC6C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
HYPK coordinates degradation of polyneddylated proteins by autophagy.
PMID: 34836490
Autophagy · 2022
1.00
2
The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound transcripts independently of Argonaute proteins.
PMID: 19383768
RNA · 2009
0.90
3
Molecular basis for GIGYF-TNRC6 complex assembly.
PMID: 36854607
RNA · 2023
0.80
4
Importance of the C-terminal domain of the human GW182 protein TNRC6C for translational repression.
PMID: 19304925
RNA · 2009
0.70
5
Mechanistic Insights into Hybridization-Based Off-Target Activity of GalNAc-siRNA Conjugates.
PMID: 40134378
Nucleic Acid Ther · 2025
0.60