WARS2

Chr 1

tryptophanyl tRNA synthetase 2, mitochondrial

Also known as: NEMMLAS, PKDYS3, TrpRS, mtTrpRS

NCBI Gene: 10352ENSG00000116874UniProt: Q9UGM6

Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Two forms of tryptophanyl-tRNA synthetase exist, a cytoplasmic form, named WARS, and a mitochondrial form, named WARS2. This gene encodes the mitochondrial tryptophanyl-tRNA synthetase. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures
UniProtParkinsonism-dystonia 3, childhood-onset

Clinical highlights

Gene-disease validity (ClinGen)
mitochondrial disease · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
9
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.67
LOEUF
DN
Mechanism· predicted
📖
GeneReview available — WARS2
Authoritative clinical overview · Recommended first read
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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?
0.67LOEUF
pLI 0.051
Z-score 2.52
OE 0.32 (0.17–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.90Z-score
OE missense 0.83 (0.73–0.94)
174 obs / 210.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.32 (0.17–0.67)
0≤0.351.4
Missense OE?0.83 (0.73–0.94)
0≤0.61.4
Synonymous OE?0.91
0≤1.21.6
LoF obs/exp: 5 / 15.8Missense obs/exp: 174 / 210.9Syn Z: 0.69

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

WARS2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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