METTL9

The protein is a methyltransferase that catalyzes 1-methylhistidine modification of target proteins containing His-x-His motifs, which may affect metal binding properties of these proteins. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically manifesting in early childhood. The gene shows high constraint against loss-of-function variants (pLI = 0.80, LOEUF = 0.45), suggesting intolerance to heterozygous protein loss.