TNRC6A

Chr 16AD

trinucleotide repeat containing adaptor 6A

Also known as: CAGH26, FAME6, GW1, GW182, TNRC6

NCBI Gene: 27327ENSG00000090905UniProt: Q8NDV7

This gene encodes a member of the trinucleotide repeat containing 6 protein family. The protein functions in post-transcriptional gene silencing through the RNA interference (RNAi) and microRNA pathways. The protein associates with messenger RNAs and Argonaute proteins in cytoplasmic bodies known as GW-bodies or P-bodies. Inhibiting expression of this gene delocalizes other GW-body proteins and impairs RNAi and microRNA-induced gene silencing. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Epilepsy, familial adult myoclonic, 6MIM #618074
AD
333
ClinVar variants
31
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TNRC6A
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 275 VUS of 333 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.
0.16LOEUF
pLI 1.000
Z-score 8.38
OE 0.09 (0.05–0.16)
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 0.90 (0.85–0.95)
951 obs / 1054.4 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.0.09 (0.05–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.85–0.95)
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.1.05
0≤1.21.6
LoF obs/exp: 9 / 98.9Missense obs/exp: 951 / 1054.4Syn Z: -0.71

ClinVar Variant Classifications

333 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic3
VUS275
Likely Benign12
Benign12
Conflicting3
28
Pathogenic
3
Likely Pathogenic
275
VUS
12
Likely Benign
12
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
0
0
3
0
3
VUS
1
266
6
2
275
Likely Benign
0
6
3
3
12
Benign
0
5
3
4
12
Conflicting
—3
Total1277439333

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

View in ClinVar →

Protein Context — Lollipop Plot

TNRC6A · 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

?Epilepsy, familial adult myoclonic, 6

MIM #618074

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy.
Ishiura H et al.·Nat Genet
2018
MiR-652-3p promotes malignancy and metastasis of cancer cells via inhibiting TNRC6A in hepatocellular carcinoma.
Chen W et al.·Biochem Biophys Res Commun
2023
LINC01082 Inhibits Non-Small Cell Lung Cancer by Targeting the miR-543/TNRC6A Axis.
Yang R et al.·Biochem Genet
2023
DNA analysis of benign adult familial myoclonic epilepsy reveals associations between the pathogenic TTTCA repeat insertion in SAMD12 and the nonpathogenic TTTTA repeat expansion in TNRC6A.
Terasaki A et al.·J Hum Genet
2021
[Molecular genetics of benign adult familial myoclonus epilepsy].
Ishiura H·Rinsho Shinkeigaku
2025Review
An SNP in the trinucleotide repeat region of the TNRC6A gene maps to a major TNGW1 autoepitope in patients with autoantibodies to GW182.
Moser JJ et al.·Adv Exp Med Biol
2013Cohort
Expression of TNRC6 (GW182) Proteins Is Not Necessary for Gene Silencing by Fully Complementary RNA Duplexes.
Liu Z et al.·Nucleic Acid Ther
2019
ADAM23 haploinsufficiency as a putative oligogenic contributor in an individual with focal epilepsy.
Krenn M et al.·Seizure
2025Case report
TTTCA repeat expansion causes familial cortical myoclonic tremor with epilepsy.
Lei XX et al.·Eur J Neurol
2019
Machine Learning of Functional Connectivity to Biotype Alcohol and Nicotine Use Disorders.
Zhu T et al.·Biol Psychiatry Cogn Neurosci Neuroimaging
2024Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
m5C modification of LINC01082 inhibits osteosarcoma progression by modulating the miR-543-TNRC6A axis.
Hu Y et al.·Transl Oncol
2025🔓 Open Access
Mechanism of LncRNA NORAD/MiR-144-3p Axis in Promoting Myocardial Ischemia-Reperfusion Injury by Targeting TNRC6A.
Wei W et al.·Int Heart J
2025Functional
Prefrontal TNRC6A mediates anxiety-like behaviour by regulating CRF through the maintenance of miR-21-3p stability.
Lu GF et al.·Neuropharmacology
2025
Hypoxic BMSC-derived exosomal miR-652-3p promotes proliferation and metastasis of hepatocarcinoma cancer cells via targeting TNRC6A.
Li M et al.·Aging (Albany NY)
2023🔓 Open Access
Circular RNA CircCDYL Regulates Proliferation and Apoptosis in Non-Small Cell Lung Cancer Cells by Sponging miR-185-5p and Upregulating TNRC6A [Retraction].
·Cancer Manag Res
2023🔓 Open Access
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