IARS2

Chr 1AR

isoleucyl-tRNA synthetase 2, mitochondrial

Also known as: CAGSSS, ILERS

The protein catalyzes the aminoacylation of tRNA with isoleucine in the mitochondrial matrix, serving as the mitochondrial isoleucine-tRNA synthetase essential for mitochondrial protein synthesis. Biallelic mutations cause an autosomal recessive multisystem disorder characterized by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia. The pathogenicity likely results from impaired mitochondrial protein synthesis due to defective aminoacylation of mitochondrial tRNAs.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.391 OMIM phenotype
Clinical SummaryIARS2
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — IARS2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.081
Z-score 5.26
OE 0.25 (0.160.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.17Z-score
OE missense 0.86 (0.800.93)
479 obs / 556.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.160.39)
00.351.4
Missense OE0.86 (0.800.93)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 14 / 56.8Missense obs/exp: 479 / 556.9Syn Z: 0.68

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

IARS2 · 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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