NSUN3

Chr 3AR

NOP2/Sun RNA methyltransferase 3

Also known as: COXPD48, MST077, MSTP077

NCBI Gene: 63899 ENSG00000178694 UniProt: Q9H649 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-N5)-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, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 48MIM #619012

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Combined oxidative phosphorylation deficiency 48; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.29

LOEUF

—

Mechanism

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

Background carrier burden — how many people carry a rare variant somewhere in NSUN3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

408 rare PASS variants

Rare truncating (LoF)

1 in 1,500

65 rare PASS variants

Rare synonymous (reference)

1 in 530

156 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NSUN3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 360	1 in 2,300
South Asian	~43k	1 in 130	1 in 1,900
Remaining (unassigned)	~30k	1 in 220	1 in 2,500
European (Finnish)	~27k	1 in 560	1 in 5,300
Admixed American	~22k	1 in 200	1 in 1,500
African / African American	~21k	1 in 120	1 in 610
East Asian	~20k	1 in 270	1 in 1,900
Ashkenazi Jewish	~13k	1 in 390	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 6.? see exons ↓