TARS3

Chr 15

threonyl-tRNA synthetase 3

Also known as: TARSL2, THRRSL, ThrRS-L

NCBI Gene: 123283 ENSG00000185418 UniProt: A2RTX5

The protein catalyzes the attachment of threonine to tRNA(Thr) and edits incorrectly charged tRNA(Thr) via its editing domain, functioning as a mitochondrial aminoacyl-tRNA synthetase essential for protein synthesis. Mutations cause autosomal recessive mitochondrial disorders affecting multiple organ systems. This gene is extremely intolerant to loss-of-function variants, indicating that even heterozygous mutations may have clinical significance.

ResearchSummary from RefSeq, UniProt

Predicted to enable threonine-tRNA ligase activity. Predicted to be involved in threonyl-tRNA aminoacylation. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.90

LOEUF

Multiple*

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?

0.90LOEUF

pLI 0.000

Z-score 2.11

OE 0.66 (0.49–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.31Z-score

OE missense 0.96 (0.88–1.04)

400 obs / 417.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.49–0.90)

0≤0.351.4

Missense OE?0.96 (0.88–1.04)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 30 / 45.3Missense obs/exp: 400 / 417.8Syn Z: -1.07

Background carrier burden — how many people carry a rare variant somewhere in TARS3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 62

1,044 rare PASS variants

Rare truncating (LoF)

1 in 790

194 rare PASS variants

Rare synonymous (reference)

1 in 91

438 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TARS3. 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 68	1 in 800
South Asian	~43k	1 in 67	1 in 470
Remaining (unassigned)	~30k	1 in 59	1 in 1,000
European (Finnish)	~27k	1 in 150	1 in 1,200
Admixed American	~22k	1 in 51	1 in 540
African / African American	~21k	1 in 46	1 in 1,000
East Asian	~20k	1 in 60	1 in 570
Ashkenazi Jewish	~13k	1 in 220	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 74	≈ 1 in 940

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): 18 of 19 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 19.? see exons ↓