KARS1

Chr 16AR

lysyl-tRNA synthetase 1

Also known as: CMTRIB, DEAPLE, DFNB89, KARS, KARS2, KRS, LEPID

NCBI Gene: 3735 ENSG00000065427 UniProt: Q15046 OMIM: 601421

Lysyl-tRNA synthetase catalyzes the attachment of lysine to its cognate tRNA and synthesizes the signaling molecule diadenosine tetraphosphate. Mutations cause autosomal recessive conditions including Charcot-Marie-Tooth disease, congenital or adult-onset deafness, and progressive leukoencephalopathy with infantile or later onset. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Lysyl-tRNA synthetase is a homodimer localized to the cytoplasm which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Charcot-Marie-Tooth disease, recessive intermediate, BMIM #613641

Deafness, autosomal recessive 89MIM #613916

Deafness, congenital, and adult-onset progressive leukoencephalopathyMIM #619196

Leukoencephalopathy, progressive, infantile-onset, with or without deafnessMIM #619147

Clinical highlights

Gene-disease validity (ClinGen)

nonsyndromic genetic hearing loss · ARLimitednot for standalone diagnostic reporting

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)

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P/LP submissions

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P/LP missense

0.91

LOEUF

LOF

Mechanism· G2P