CARS1

Chr 11AR

cysteinyl-tRNA synthetase 1

Also known as: CARS, CYSRS, MCDDBH, MDBH, MGC:11246

The protein catalyzes the ATP-dependent ligation of cysteine to tRNA(Cys) as a class 1 aminoacyl-tRNA synthetase essential for protein synthesis. Mutations cause microcephaly, developmental delay, and brittle hair syndrome with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variation (LOEUF 0.494), reflecting its essential cellular role.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.491 OMIM phenotype
Clinical SummaryCARS1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.000
Z-score 4.31
OE 0.32 (0.210.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.20Z-score
OE missense 0.85 (0.780.92)
411 obs / 485.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.210.49)
00.351.4
Missense OE0.85 (0.780.92)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 15 / 46.8Missense obs/exp: 411 / 485.1Syn Z: 0.30
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCARS1-related microcephaly, developmental delay, and brittle hair and nailsLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6454th %ile
GOF
0.5661th %ile
LOF
0.3552th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CARS1 · 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

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC