TRMT12

The protein catalyzes transfer of amino acid groups from S-adenosyl-L-methionine during wybutosine biosynthesis, producing a hypermodified guanosine that stabilizes codon-anticodon interactions in phenylalanine tRNA during ribosomal protein synthesis. Mutations cause intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, inherited in an autosomal recessive pattern. The gene shows significant constraint against loss-of-function variants (LOEUF 0.53), indicating intolerance to complete protein loss.