LARS2

Chr 3AR

leucyl-tRNA synthetase 2, mitochondrial

Also known as: HLASA, LEURS, PRLTS4, mtLeuRS

The protein is mitochondrial leucyl-tRNA synthetase, which catalyzes the attachment of leucine to its cognate tRNA for mitochondrial protein synthesis. Biallelic mutations cause autosomal recessive disorders including hydrops with lactic acidosis and sideroblastic anemia, and Perrault syndrome 4 (ovarian dysgenesis with sensorineural hearing loss). Pathogenicity results from impaired mitochondrial protein synthesis leading to mitochondrial dysfunction.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.862 OMIM phenotypes
Clinical SummaryLARS2
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Gene-Disease Validity (ClinGen)
Perrault syndrome · 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.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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 2.40
OE 0.64 (0.490.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.33Z-score
OE missense 0.83 (0.770.90)
427 obs / 511.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.64 (0.490.86)
00.351.4
Missense OE0.83 (0.770.90)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 34 / 52.8Missense obs/exp: 427 / 511.7Syn Z: 0.48

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LARS2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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