CARS2

Chr 13

cysteinyl-tRNA synthetase 2, mitochondrial

Also known as: COXPD27, cysRS

NCBI Gene: 79587ENSG00000134905UniProt: Q9HA77

This gene encodes a putative member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of cysteine to tRNA molecules. A splice-site mutation in this gene has been associated with a novel progressive myoclonic epilepsy disease with similar symptoms to MERRF syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCombined oxidative phosphorylation deficiency 27

Clinical highlights

Gene-disease validity (ClinGen)
mitochondrial disease · ARModerateconsider for supplementary testing
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
3
Active trials
23
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.84
LOEUF
LOF
Mechanism· G2P
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?
0.84LOEUF
pLI 0.000
Z-score 2.23
OE 0.55 (0.37–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.25Z-score
OE missense 0.96 (0.88–1.05)
318 obs / 330.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.55 (0.37–0.84)
0≤0.351.4
Missense OE?0.96 (0.88–1.05)
0≤0.61.4
Synonymous OE?1.08
0≤1.21.6
LoF obs/exp: 16 / 28.9Missense obs/exp: 318 / 330.8Syn Z: -0.73

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CARS2 · 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