NSUN2

Chr 5AR

NOP2/Sun RNA methyltransferase 2

Also known as: MISU, MRT5, SAKI, TRM4

NCBI Gene: 54888 ENSG00000037474 UniProt: Q08J23 OMIM: 610916

The protein is an RNA cytosine methyltransferase that modifies cytosines in tRNAs, mRNAs, and other RNAs to stabilize these molecules and regulate protein synthesis. Mutations cause autosomal recessive intellectual developmental disorder. The gene is highly intolerant to loss-of-function variants (pLI near 0, LOEUF 0.531), suggesting that complete protein loss severely disrupts cellular RNA metabolism and normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a methyltransferase that catalyzes the methylation of cytosine to 5-methylcytosine (m5C) at position 34 of intron-containing tRNA(Leu)(CAA) precursors. This modification is necessary to stabilize the anticodon-codon pairing and correctly translate the mRNA. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Mar 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 5MIM #611091

Clinical highlights

Gene-disease validity (ClinGen)

RASopathy · ARDisputedevidence questions this relationship2 gene-disease associations curated in total

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

198

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.53

LOEUF

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Mechanism