NARS1

Chr 18

asparaginyl-tRNA synthetase 1

Also known as: ASNRS, NARS, NEDMILEG, NEDMILG

NCBI Gene: 4677 ENSG00000134440 UniProt: O43776

The protein catalyzes the attachment of asparagine to tRNA(Asn) and plays an essential role in cerebral cortex development by regulating radial glial cell proliferation. Mutations cause neurodevelopmental disorders with microcephaly, impaired language, and gait abnormalities, with some patients also presenting with epilepsy. The gene shows both autosomal recessive and autosomal dominant inheritance patterns and is highly constrained against loss-of-function variants.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Asparaginyl-tRNA synthetase is localized to the cytoplasm and belongs to the class II family of tRNA synthetases. The N-terminal domain represents the signature sequence for the eukaryotic asparaginyl-tRNA synthetases. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities

UniProtNeurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities

Clinical highlights

Gene-disease validity (ClinGen)

neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities · ADModerateconsider for supplementary testing2 gene-disease associations curated in total

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

Multiple*

Mechanism· G2P

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GeneReview available — NARS1