TNRC6B

Chr 22AD

trinucleotide repeat containing adaptor 6B

Also known as: GDSBA

NCBI Gene: 23112ENSG00000100354UniProt: Q9UPQ9

Enables RNA binding activity. Involved in positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; positive regulation of nuclear-transcribed mRNA poly(A) tail shortening; and regulatory ncRNA-mediated gene silencing. Acts upstream of with a positive effect on miRNA-mediated gene silencing by inhibition of translation. Predicted to be located in cytosol. Predicted to be active in P-body and nucleoplasm. Implicated in subserous uterine fibroid and uterine fibroid. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Global developmental delay with speech and behavioral abnormalitiesMIM #619243
AD
655
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TNRC6B
⚡
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
655 total variants — no pathogenic classifications of 655 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.
0.17LOEUF
pLI 1.000
Z-score 7.95
OE 0.10 (0.06–0.17)
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.
2.87Z-score
OE missense 0.74 (0.70–0.79)
733 obs / 987.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.10 (0.06–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.70–0.79)
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.1.01
0≤1.21.6
LoF obs/exp: 9 / 90.7Missense obs/exp: 733 / 987.1Syn Z: -0.22

ClinVar Variant Classifications

655 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

TNRC6B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TNRC6B-related neurodevelopmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Global developmental delay with speech and behavioral abnormalities

MIM #619243

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pathogenic variants in TNRC6B cause a genetic disorder characterised by developmental delay/intellectual disability and a spectrum of neurobehavioural phenotypes including autism and ADHD.
Granadillo JL et al.·J Med Genet
2020
Novel variants in TNRC6B cause global developmental delay with speech and behavioral abnormalities, short stature, low body weight, café-au-lait spots, and metabolic abnormality.
Yang Q et al.·Mol Genet Genomic Med
2024Case report
A Case Report: Co-Occurrence of TNRC6B Gene Variant and Xq28 Microdeletion Syndrome With Comprehensive Literature Review.
Deng Y et al.·Birth Defects Res
2025Review
Association of BET1L and TNRC6B with uterine leiomyoma risk and its relevant clinical features in Han Chinese population.
Liu B et al.·Sci Rep
2018
Epilepsy and Autism spectrum disorder caused by a pathogenic variant in TNRC6B.
Bellido-Cuéllar S et al.·Seizure
2023
Circular RNA circ-TNRC6B inhibits the proliferation and invasion of esophageal squamous cell carcinoma cells by regulating the miR-452-5p/DAG1 axis.
Xu R et al.·Mol Oncol
2023
Mendelian non-syndromic and syndromic hearing loss genes contribute to presbycusis.
Cornejo-Sanchez DM et al.·Eur J Hum Genet
2025
Identification of the synonymous variant c.3141G > A in TNRC6B gene that altered RNA splicing by minigene assay.
Zhou F et al.·Mol Biol Rep
2024Case report
Genetic Determinants of Colonic Diverticulosis-A Systematic Review.
Nehring P et al.·Genes (Basel)
2025Review
Exome-wide screening identifies novel rare risk variants for major depression disorder.
Cheng S et al.·Mol Psychiatry
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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