DARS2

Chr 1AR

aspartyl-tRNA synthetase 2, mitochondrial

The protein is a mitochondrial aminoacyl-tRNA synthetase that specifically charges aspartyl-tRNA, essential for mitochondrial protein synthesis. Autosomal recessive mutations cause leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) and axonal Charcot-Marie-Tooth disease type 2LL through impaired mitochondrial translation. Disease mechanisms likely involve loss of enzyme function leading to defective mitochondrial protein synthesis and subsequent energy metabolism defects.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.922 OMIM phenotypes
Clinical SummaryDARS2
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.92LOEUF
pLI 0.000
Z-score 1.97
OE 0.66 (0.480.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.19Z-score
OE missense 0.82 (0.740.90)
285 obs / 347.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.66 (0.480.92)
00.351.4
Missense OE0.82 (0.740.90)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 25 / 38.2Missense obs/exp: 285 / 347.7Syn Z: 0.96
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongDARS2-related leukoencephalopathy with brainstem and spinal cord involvement and lactate elevationLOFAR

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

DN
0.6939th %ile
GOF
0.5660th %ile
LOF
0.3164th %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

DARS2 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →