DARS1

Chr 2AR

aspartyl-tRNA synthetase 1

Also known as: DARS, HBSL, aspRS

The protein ligates L-aspartate to tRNA(Asp) as part of a multienzyme complex essential for protein synthesis. Biallelic mutations cause hypomyelination with brainstem and spinal cord involvement and leg spasticity, inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant-negative effects that disrupt normal aminoacyl-tRNA synthetase function.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.681 OMIM phenotype
Clinical SummaryDARS1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.000
Z-score 2.96
OE 0.44 (0.290.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.75Z-score
OE missense 0.87 (0.780.97)
235 obs / 269.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.290.68)
00.351.4
Missense OE0.87 (0.780.97)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 14 / 32.1Missense obs/exp: 235 / 269.5Syn Z: 0.11
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveDARS1-related hypomyelination with brain stem and spinal cord involvement and leg spasticityOTHERAR

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

DN
0.6937th %ile
GOF
0.5856th %ile
LOF
0.3163th %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

DARS1 · 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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