TNRC6B

Chr 22AD

trinucleotide repeat containing adaptor 6B

Also known as: GDSBA

NCBI Gene: 23112 ENSG00000100354 UniProt: Q9UPQ9 OMIM: 610740

TNRC6B encodes a scaffolding protein essential for microRNA-mediated gene silencing and mRNA degradation, associating with argonaute proteins and recruiting deadenylase complexes to regulate gene expression. Mutations cause autosomal dominant global developmental delay with speech and behavioral abnormalities. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.17), indicating that functional copies are critical for normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Global developmental delay with speech and behavioral abnormalitiesMIM #619243

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· G2P