TNRC6A

Chr 16AD

trinucleotide repeat containing adaptor 6A

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

NCBI Gene: 27327ENSG00000090905UniProt: Q8NDV7OMIM: 610739

The protein functions as a scaffolding component in RNA-mediated gene silencing, recruiting deadenylase complexes and associating with argonaute proteins to enable microRNA and siRNA-mediated translational repression and mRNA cleavage. Mutations cause autosomal dominant neurodevelopmental disorder with seizures, developmental delay, and intellectual disability. This gene is highly intolerant to loss-of-function mutations, indicating that proper dosage is critical for normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismADLOEUF 0.161 OMIM phenotype
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
2 unique Pathogenic / Likely Pathogenic· 152 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
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
1.13Z-score
OE missense 0.90 (0.85–0.95)
951 obs / 1054.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.05–0.16)
0≤0.351.4
Missense OE0.90 (0.85–0.95)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 9 / 98.9Missense obs/exp: 951 / 1054.4Syn Z: -0.71
DN
0.2199th %ile
GOF
0.3193th %ile
LOF
0.87top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.16

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
VUS152
Likely Benign6
Benign1
Conflicting3
2
Pathogenic
152
VUS
6
Likely Benign
1
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
2
0
2
Likely Pathogenic
0
0
0
0
0
VUS
1
150
0
1
152
Likely Benign
0
4
0
2
6
Benign
0
1
0
0
1
Conflicting
—3
Total115523164

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Downregulation of Long Noncoding RNA LINC00261 Attenuates Myocardial Infarction through the miR-522-3p/Trinucleotide Repeat-Containing Gene 6a (TNRC6A) Axis
Jiang C et al.·Cardiovasc Ther
2021
Distinct temporal expression of the GW182 paralog TNRC6A in neurons regulates dendritic arborization.
Nawalpuri B et al.·J Cell Sci
2021
Circular RNA CircCDYL Regulates Proliferation and Apoptosis in Non-Small Cell Lung Cancer Cells by Sponging miR-185-5p and Upregulating TNRC6A
Bian WX et al.·Cancer Manag Res
2021
Integrative Analysis of Deregulated miRNAs Reveals Candidate Molecular Mechanisms Linking H. pylori Infected Peptic Ulcer Disease with Periodontitis
Li N et al.·Dis Markers
2022Functional
circRNA circ_102049 Implicates in Pancreatic Ductal Adenocarcinoma Progression through Activating CD80 by Targeting miR-455-3p
Zhu J et al.·Mediators Inflamm
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search 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
2025Open 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)
2023Open 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
2023Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients