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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TNRC6A
trinucleotide repeat containing adaptor 6A
Chromosome 16 · 16p12.1
NCBI Gene: 27327Ensembl: ENSG00000090905.20HGNC: HGNC:11969UniProt: Q8NDV7
168PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
P-bodyprotein bindingRISC complexprotein-macromolecule adaptor activityintelligencemyoclonic epilepsysmoking initiationchronic obstructive pulmonary disease
✦AI Summary

TNRC6A (trinucleotide repeat containing adaptor 6A) is a critical scaffolding protein in the microRNA-mediated gene silencing pathway. The protein functions as an adaptor that bridges Argonaute proteins bound to target mRNAs with deadenylase complexes, facilitating both translational repression and mRNA degradation 1. TNRC6A contains N-terminal GW-repeat domains that interact with all four human Argonaute proteins (AGO1-AGO4) and C-terminal silencing domains that operate independently of Argonaute binding to promote mRNA silencing through deadenylation and protein expression changes 1. The protein exhibits nuclear-cytoplasmic shuttling behavior and can navigate Argonaute proteins into the nucleus for miRNA-mediated gene silencing 2. Post-translational phosphorylation of TNRC6A regulates its interaction with the CCR4-NOT deadenylase complex, with specific phosphorylation patterns either enhancing or suppressing these interactions 3. Clinically, TNRC6A is associated with benign adult familial myoclonic epilepsy (BAFME), caused by pathogenic expansions of TTTCA and TTTTA repeats in the gene's intronic regions 45. These repeat expansions demonstrate dynamic variability and correlate with disease severity and onset age, representing a novel mechanism of neurological disease pathogenesis through non-coding repeat expansion.

Sources cited
1
TNRC6A functions as scaffolding protein with N-terminal Argonaute-binding domains and C-terminal silencing domains that promote mRNA silencing through deadenylation
PMID: 19383768
2
TNRC6A is a nuclear-cytoplasmic shuttling protein that can navigate Argonaute proteins into the nucleus for miRNA-mediated gene silencing
PMID: 23150874
3
Post-translational phosphorylation of TNRC6A regulates its interaction with the CCR4-NOT deadenylase complex
PMID: 33668648
4
TNRC6A is associated with benign adult familial myoclonic epilepsy caused by expansions of TTTCA and TTTTA repeats in intronic regions
PMID: 29507423
5
TNRC6A repeat expansions are dynamic and correlate with disease severity and onset age in familial adult myoclonic epilepsy
PMID: 37021642
Disease Associationsⓘ21
intelligenceOpen Targets
0.48Moderate
myoclonic epilepsyOpen Targets
0.48Moderate
smoking initiationOpen Targets
0.43Moderate
chronic obstructive pulmonary diseaseOpen Targets
0.42Moderate
shortness of breathOpen Targets
0.39Weak
attention deficit hyperactivity disorderOpen Targets
0.37Weak
osteomyelitisOpen Targets
0.37Weak
benign adult familial myoclonic epilepsyOpen Targets
0.37Weak
epilepsy, familial adult myoclonicOpen Targets
0.37Weak
type 2 diabetes mellitusOpen Targets
0.37Weak
atrial fibrillationOpen Targets
0.36Weak
bone diseaseOpen Targets
0.35Weak
DyspneaOpen Targets
0.35Weak
mathematical abilityOpen Targets
0.33Weak
smoking cessationOpen Targets
0.32Weak
diabetes mellitusOpen Targets
0.31Weak
obstructive sleep apneaOpen Targets
0.31Weak
autism spectrum disorderOpen Targets
0.30Weak
obesityOpen Targets
0.28Weak
hypertensionOpen Targets
0.28Weak
Epilepsy, familial adult myoclonic, 6UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DDX3XProtein interaction100%DDX6Protein interaction100%DHX9Protein interaction100%EIF4EProtein interaction100%FMR1Protein interaction100%MOV10Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Liver
84%
Heart
72%
Bone Marrow
65%
Lung
56%
Brain
39%
Gene Interaction Network
Click a node to explore
TNRC6ADDX3XDDX6DHX9EIF4EFMR1MOV10
PROTEIN STRUCTURE
Preparing viewer…
PDB7RUP · 1.23 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.26Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.20 [0.16–0.26]
RankingsWhere TNRC6A stands among ~20K protein-coding genes
  • #2,662of 20,598
    Most Researched168 · top quartile
  • #814of 17,882
    Most Constrained (LOEUF)0.26 · top 5%
Genes detectedTNRC6A
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP.
PMID: 20371350
Cell · 2010
1.00
2
Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy.
PMID: 29507423
Nat Genet · 2018
0.90
3
Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene silencing in the nucleus.
PMID: 23150874
RNA · 2013
0.80
4
RNA helicase DDX6 and scaffold protein GW182 in P-bodies promote biogenesis of stress granules.
PMID: 37427791
Nucleic Acids Res · 2023
0.72
5
The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound transcripts independently of Argonaute proteins.
PMID: 19383768
RNA · 2009
0.70