Tnrc18, a chromatin regulator, is involved in crucial biological processes. Its carboxy-terminal bromo-adjacent homology (BAH) domain acts as an H3K9me3-specific reader, and it recruits co-repressors like HDAC-Sin3-NCoR complexes through its amino-terminal segment. This is significant for the epigenetic regulation of endogenous retrotransposons, host genome integrity, transcriptomic regulation, immunity, and development [1].

In mice, point mutagenesis disrupting the TNRC18(BAH)-mediated H3K9me3 engagement led to neonatal death. In multiple mammalian cell models, it caused derepressed expression of ERVs, affecting the cis-regulatory element landscape and gene-expression programmes [1]. Also, a mutation in TNRC18 was identified as a possible cause of Fazio-Londe disease in a patient [2]. TNRC18-RARA fusion has been found in acute promyelocytic leukemia lacking the classic PML-RARA fusion, and patients with this fusion may be resistant to standard differentiation induction therapy [3,5,7]. A balanced translocation disrupting the TNRC18 gene was associated with neurodevelopmental delay in a patient, with reduced TNRC18 expression [4]. Genome-wide association studies have associated TNRC18 with anterior uveitis, and SNPs at the TNRC18 locus are also associated with other immunity-related phenotypes [6].

In summary, Tnrc18 is essential for the silencing of endogenous retrotransposons through its interaction with H3K9me3. Its disruption is linked to various diseases, including neonatal lethality in mice, Fazio-Londe disease, acute promyelocytic leukemia, and anterior uveitis. Studies on Tnrc18 using mouse models and patient samples have provided insights into its role in these disease conditions, highlighting its importance in understanding disease mechanisms and potential therapeutic development.