TARS2

Chr 1AR

threonyl-tRNA synthetase 2, mitochondrial

Also known as: COXPD21, TARSL1, thrRS

NCBI Gene: 80222ENSG00000143374UniProt: Q9BW92OMIM: 612805

The encoded protein is a mitochondrial aminoacyl-tRNA synthetase that charges tRNA with threonine for mitochondrial protein synthesis. Biallelic mutations cause combined oxidative phosphorylation deficiency 21, an autosomal recessive disorder affecting mitochondrial respiratory chain function. The pathogenic mechanism involves dominant-negative effects that disrupt mitochondrial translation and oxidative phosphorylation.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.841 OMIM phenotype
Clinical Summary— TARS2
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 140 VUS of 368 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.000
Z-score 2.39
OE 0.61 (0.44–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.77Z-score
OE missense 0.76 (0.69–0.83)
323 obs / 425.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.61 (0.44–0.84)
0≤0.351.4
Missense OE0.76 (0.69–0.83)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 26 / 42.9Missense obs/exp: 323 / 425.8Syn Z: 0.15
DN
0.6936th %ile
GOF
0.5856th %ile
LOF
0.2871th %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

368 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic19
VUS140
Likely Benign119
Benign50
Conflicting10
12
Pathogenic
19
Likely Pathogenic
140
VUS
119
Likely Benign
50
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
4
12
2
1
19
VUS
7
117
15
1
140
Likely Benign
0
6
56
57
119
Benign
0
2
43
5
50
Conflicting
—10
Total1113712864350

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TARS2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients