AARS1

Chr 16ADAR

alanyl-tRNA synthetase 1

Also known as: AARS, CMT2N, DEE29, EIEE29, HDLS2, TTD8

NCBI Gene: 16 ENSG00000090861 UniProt: P49588 OMIM: 601065

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The human alanyl-tRNA synthetase (AARS) belongs to a family of tRNA synthases, of the class II enzymes. Class II tRNA synthases evolved early in evolution and are highly conserved. This is reflected by the fact that 498 of the 968-residue polypeptide human AARS shares 41% identity witht the E.coli protein. tRNA synthases are the enzymes that interpret the RNA code and attach specific aminoacids to the tRNAs that contain the cognate trinucleotide anticodons. They consist of a catalytic domain which interacts with the amino acid acceptor-T psi C helix of the tRNA, and a second domain which interacts with the rest of the tRNA structure. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Leukoencephalopathy, hereditary diffuse, with spheroids 2MIM #619661

Charcot-Marie-Tooth disease, axonal, type 2NMIM #613287

Developmental and epileptic encephalopathy 29MIM #616339

Trichothiodystrophy 8, nonphotosensitiveMIM #619691

Clinical highlights

Gene-disease validity (ClinGen)

Charcot-Marie-Tooth disease axonal type 2N · ADDefinitivesufficient evidence for diagnostic panels3 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.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

0.62

LOEUF

LOF

Mechanism· G2P

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GeneReview available — AARS1