NARS2

Chr 11AR

asparaginyl-tRNA synthetase 2, mitochondrial

Also known as: DFNB94, SLM5, asnRS

The protein catalyzes the ligation of asparagine to tRNA molecules in the mitochondrial matrix, which is essential for mitochondrial protein biosynthesis. Mutations cause combined oxidative phosphorylation deficiency 24 and autosomal recessive deafness through an autosomal recessive inheritance pattern. The pathogenic mechanism appears to be dominant negative, where mutant proteins interfere with normal mitochondrial protein synthesis.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.862 OMIM phenotypes
Clinical SummaryNARS2
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

3 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — NARS2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.12
OE 0.57 (0.380.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.76Z-score
OE missense 1.13 (1.031.25)
292 obs / 257.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.380.86)
00.351.4
Missense OE1.13 (1.031.25)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 16 / 28.2Missense obs/exp: 292 / 257.7Syn Z: -1.04
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNARS2-related oxidative phosphorylation deficiencyLOFAR

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

DN
0.76top 25%
GOF
0.5759th %ile
LOF
0.2483th %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

NARS2 · 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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