IARS2

Chr 1AR

isoleucyl-tRNA synthetase 2, mitochondrial

Also known as: CAGSSS, ILERS

NCBI Gene: 55699 ENSG00000067704 UniProt: Q9NSE4 OMIM: 612801

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAS, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Two forms of isoleucine-tRNA synthetase exist, a cytoplasmic form and a mitochondrial form. This gene encodes the mitochondrial isoleucine-tRNA synthetase which belongs to the class-I aminoacyl-tRNA synthetase family. [provided by RefSeq, Dec 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasiaMIM #616007

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.39

LOEUF

LOF

Mechanism· G2P

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GeneReview available — IARS2