TRMT2A

Chr 22

tRNA methyltransferase 2A

Also known as: HTF9C

The encoded protein is an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of 5-methyl-uridine in tRNAs and some mRNAs, primarily methylating uridine at position 54 in cytosolic tRNAs. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. The gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.92
Clinical SummaryTRMT2A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.92LOEUF
pLI 0.000
Z-score 1.88
OE 0.61 (0.420.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.13Z-score
OE missense 1.02 (0.941.11)
405 obs / 397.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.61 (0.420.92)
00.351.4
Missense OE1.02 (0.941.11)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 17 / 27.7Missense obs/exp: 405 / 397.6Syn Z: -2.01
DN
0.6745th %ile
GOF
0.5268th %ile
LOF
0.3065th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TRMT2A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC