TRMT5

Chr 14AR

tRNA methyltransferase 5

Also known as: COXPD26, KIAA1393, PNSED, TRM5

NCBI Gene: 57570 ENSG00000126814 UniProt: Q32P41 OMIM: 611023

TRMT5 encodes a methyltransferase that specifically methylates guanosine-37 in various tRNAs, which is the first step in biosynthesis of wybutosine, a modified base required for accurate decoding during protein translation. Biallelic mutations cause autosomal recessive peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.588), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

tRNAs contain as many as 13 or 14 nucleotides that are modified posttranscriptionally by enzymes that are highly specific for particular nucleotides in the tRNA structure. TRMT5 methylates the N1 position of guanosine-37 (G37) in selected tRNAs using S-adenosyl methionine (Brule et al., 2004 [PubMed 15248782]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delayMIM #616539

Clinical highlights

Gene-disease validity (ClinGen)

mitochondrial disease · ARDefinitivesufficient evidence for diagnostic panels

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

0.59

LOEUF

Mechanism· predicted