TRMT10B

Chr 9

tRNA methyltransferase 10B

Also known as: RG9MTD3, bA3J10.9

NCBI Gene: 158234 ENSG00000165275 UniProt: Q6PF06

The protein is an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of N(1)-methylguanine at position 9 in tRNAs and is involved in protein insertion into the mitochondrial inner membrane as part of the TIM22 complex. Mutations cause microcephaly, short stature, and limb defects with autosomal recessive inheritance. The gene shows extremely high constraint against loss-of-function variants (pLI near 1.0), indicating that complete loss of function is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt

Enables tRNA (guanosine(9)-N1)-methyltransferase activity. Involved in protein insertion into mitochondrial inner membrane. Located in cytosol and mitochondrial inner membrane. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.49

OE 0.62 (0.39–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.30Z-score

OE missense 0.93 (0.82–1.07)

151 obs / 161.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.39–1.02)

0≤0.351.4

Missense OE?0.93 (0.82–1.07)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 11 / 17.8Missense obs/exp: 151 / 161.7Syn Z: -0.22

Background carrier burden — how many people carry a rare variant somewhere in TRMT10B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

388 rare PASS variants

Rare truncating (LoF)

1 in 340

136 rare PASS variants

Rare synonymous (reference)

1 in 210

142 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TRMT10B; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 310	1 in 1,200
South Asian	~43k	1 in 140	1 in 560
Remaining (unassigned)	~30k	1 in 200	1 in 1,400
European (Finnish)	~27k	1 in 470	1 in 3,300
Admixed American	~22k	1 in 140	1 in 530
African / African American	~21k	1 in 130	1 in 490
East Asian	~20k	1 in 160	1 in 880
Ashkenazi Jewish	~13k	1 in 510	1 in 1,300
Middle Eastern	~2,884	1 in 120	1 in 480

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓