METTL9

Chr 16

methyltransferase 9, His-X-His N1(pi)-histidine

Also known as: CGI-81, DREV, DREV1, PAP1, hMETTL9

NCBI Gene: 51108 ENSG00000197006 UniProt: Q9H1A3

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.

ResearchSummary from RefSeq, UniProt

Enables protein-L-histidine N-pros-methyltransferase activity. Predicted to be involved in methylation. Is active in endoplasmic reticulum and mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.45

LOEUF

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Mechanism

Some data sources returned errors (1)

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