AARS1

Chr 16ADAR

alanyl-tRNA synthetase 1

Alanyl-tRNA synthetase catalyzes the attachment of alanine to tRNA(Ala) and edits incorrectly charged tRNA molecules, playing an essential role in protein synthesis. Mutations cause autosomal dominant or recessive disorders including Charcot-Marie-Tooth disease type 2N, developmental and epileptic encephalopathy with early onset, leukoencephalopathy with spheroids, and nonphotosensitive trichothiodystrophy. This gene is highly constrained against loss-of-function variants (LOEUF 0.617), reflecting its critical cellular function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.624 OMIM phenotypes
Clinical SummaryAARS1
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Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease axonal type 2N · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

3 total gene-disease associations curated

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
0.62LOEUF
pLI 0.000
Z-score 3.75
OE 0.43 (0.310.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.05Z-score
OE missense 0.99 (0.931.07)
538 obs / 541.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.310.62)
00.351.4
Missense OE0.99 (0.931.07)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 22 / 50.9Missense obs/exp: 538 / 541.4Syn Z: -0.96
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongAARS1-related early-onset epileptic encephalopathy with persistent myelination defectLOFAR

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

DN
0.6649th %ile
GOF
0.6248th %ile
LOF
0.3358th %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.

Literature Evidence

DNThis suggests that neuropathy-associated AARS1 variants exert a dominant-negative effect, which supports a common, loss-of-function mechanism for ARS-mediated dominant peripheral neuropathy.PMID:37010095

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AARS1 · 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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