TRPT1

Chr 11

tRNA phosphotransferase 1

NCBI Gene: 83707 ENSG00000149743 UniProt: Q86TN4 OMIM: 610470

The protein catalyzes the final step of tRNA splicing by transferring the splice junction 2'-phosphate from ligated tRNA to NAD to produce ADP-ribose 1''-2'' cyclic phosphate. Mutations in this gene cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in infancy or early childhood. This gene shows low constraint against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected patients.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable tRNA 2'-phosphotransferase activity. Predicted to be involved in tRNA splicing, via endonucleolytic cleavage and ligation. Predicted to act upstream of or within regulation of protein kinase activity. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.00

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.00LOEUF

pLI 0.002

Z-score 1.58

OE 0.51 (0.28–1.00)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.55Z-score

OE missense 0.87 (0.76–1.01)

129 obs / 147.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.28–1.00)

0≤0.351.4

Missense OE?0.87 (0.76–1.01)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 6 / 11.9Missense obs/exp: 129 / 147.9Syn Z: 0.49

Background carrier burden — how many people carry a rare variant somewhere in TRPT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

356 rare PASS variants

Rare truncating (LoF)

1 in 1,500

83 rare PASS variants

Rare synonymous (reference)

1 in 450

164 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRPT1. 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 190	1 in 1,400
South Asian	~43k	1 in 180	1 in 1,600
Remaining (unassigned)	~30k	1 in 95	1 in 1,800
European (Finnish)	~27k	1 in 1,600	1 in 2,400
Admixed American	~22k	1 in 150	1 in 1,200
African / African American	~21k	1 in 170	1 in 2,400
East Asian	~20k	1 in 240	1 in 1,200
Ashkenazi Jewish	~13k	1 in 800	1 in 1,800
Middle Eastern	~2,884	1 in 260	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓