tRNA (guanine-N7)-methyltransferase non-catalytic subunit WDR4 (WDR4)

tRNA (guanine-N7)-methyltransferase non-catalytic subunit WDR4 (WDR4) is the non-catalytic, regulatory subunit of the METTL1-WDR4 complex that mediates methylation of guanine at the N7 position (m^7G) at position 46 in tRNAs in humans[1][2][3]. The modification is essential for tRNA stability and efficient protein synthesis. WDR4 is a WD repeat-containing protein that acts as a molecular scaffold—facilitating correct folding, efficient cofactor (SAM) binding, and tRNA substrate recognition by METTL1. Loss-of-function mutations in WDR4 result in reduced m^7G46 modification and have been linked to disorders such as primordial dwarfism and brain malformation; dysregulation in this complex is also associated with cancer. WDR4 itself does not catalyze methyl transfer but is required for the enzymatic activity of the complex and maintaining METTL1 stability[1][2][3]. No approved drugs are known to target WDR4 directly; however, its essential role in RNA modification and human disease suggests it may become a relevant target for future drug discovery[1][3].

Other names

WD repeat domain 4WD repeat-containing protein 4protein Wuho homologTRM82TRMT82hWHGAMOS6MIGSBWD repeat domain 4 METTL1 scaffold proteinTRM82 tRNA methyltransferase 82 homolog (S. cerevisiae)

Scaffold/co-factor for tRNA methyltransferase activity (enables METTL1's methylation of tRNA at guanine N7 position)