NSUN3

Chr 3AR

NOP2/Sun RNA methyltransferase 3

Also known as: COXPD48, MST077, MSTP077

NCBI Gene: 63899 ENSG00000178694 OMIM: 617491

NSUN3 encodes a mitochondrial tRNA methyltransferase that methylates cytosine at the wobble position of mitochondrial tRNA(Met), enabling recognition of both AUG and AUA codons during mitochondrial protein synthesis. Mutations cause combined oxidative phosphorylation deficiency 48, a mitochondrial disorder affecting cellular energy production. The condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables tRNA (cytidine-5-)-methyltransferase activity. Involved in regulation of mitochondrial translation and tRNA wobble base cytosine methylation. Located in mitochondrial matrix. Implicated in combined oxidative phosphorylation deficiency 48. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

ARLOEUF 1.291 OMIM phenotype

Clinical Summary— NSUN3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 88 VUS of 145 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.29LOEUF

pLI 0.000

Z-score 0.67

OE 0.82 (0.54–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.31Z-score

OE missense 0.93 (0.82–1.06)

164 obs / 175.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.82 (0.54–1.29)

0≤0.351.4

Missense OE?0.93 (0.82–1.06)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 14 / 17.0Missense obs/exp: 164 / 175.4Syn Z: 0.92

ClinVar Variant Classifications

145 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic1

VUS88

Likely Benign41

Benign4

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	2	0	0	4
Likely Pathogenic	1	0	0	0	1
VUS	7	77	4	0	88
Likely Benign	0	5	11	25	41
Benign	0	1	1	2	4
Conflicting	—				1
Total	10	85	16	27	139

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

11 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap NSUN3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →