WARS1

Chr 14

tryptophanyl-tRNA synthetase 1

Also known as: GAMMA-2, HMN9, HMND9, IFI53, IFP53, NEDMSBA, WARS

NCBI Gene: 7453ENSG00000140105UniProt: P23381

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. Tryptophanyl-tRNA synthetase (WARS) catalyzes the aminoacylation of tRNA(trp) with tryptophan and is induced by interferon. Tryptophanyl-tRNA synthetase belongs to the class I tRNA synthetase family. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeuronopathy, distal hereditary motor, autosomal dominant 9
UniProtNeurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities

Clinical highlights

Gene-disease validity (ClinGen)
distal hereditary motor neuropathy · ADLimitednot for standalone diagnostic reporting
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.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
20
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.49
LOEUF
DN
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
Moderate LoF intolerance
LoF Constraint?
0.49LOEUF
pLI 0.303
Z-score 3.28
OE 0.23 (0.12–0.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.99Z-score
OE missense 0.67 (0.59–0.75)
188 obs / 282.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.23 (0.12–0.49)
0≤0.351.4
Missense OE?0.67 (0.59–0.75)
0≤0.61.4
Synonymous OE?0.88
0≤1.21.6
LoF obs/exp: 5 / 21.4Missense obs/exp: 188 / 282.2Syn Z: 1.01

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

WARS1 · protein map & ClinVar variants

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

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