Optic neuropathy

Gene: NSUN3

Green List (high evidence)

Comment on list classification: As reviewed by Neringa Jurkute, there are at least 6 unrelated families reported in literature with optic neuropathy (isolated or syndromic) and biallelic NSUN3 variants. Hence, this gene can be promoted to Green on Optic neuropathy at the next update.

Created: 27 May 2026, 9:59 a.m. | Last Modified: 27 May 2026, 9:59 a.m.

Panel Version: 6.29

De Muiknck et al. 2024, PMID: 38790159: proband with childhood-onset bilateral OA and nystagmus; hom for frameshift variant c.349_352dup p.(Ala118Glufs*45) in NSUN3 (both parents het and unaffected sib het).

Jurkute et al. 2025, PMID: 40465263: 5 families (8 affected individuals) with biallelic variants in NSUN3 – phenotype from mild isolated OA to severe multisystem disease (“almost all” with OA).

NSUN3 is associated with AR Combined oxidative phosphorylation deficiency 48, OMIM:619012 (OMIM accessed 27th May 2026).

Created: 27 May 2026, 9:57 a.m. | Last Modified: 27 May 2026, 9:57 a.m.

Panel Version: 6.28

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 48, OMIM:619012

Publications

• 38790159
• 40465263

Green List (high evidence)

PMID: 40465263
Biallelic NSUN3 variants were reported to be associated with an early onset severe mitochondrial disorder characterized by combined mitochondrial respiratory chain complex deficiency.
2 individuals from the paper presented with LHON-like phenotype;
5 with attenuated
2 syndromic
Optic atrophy was unifying feature.

PMID: 38790159
Mutations in NSUN3, a Mitochondrial Methyl Transferase Gene, Cause Inherited Optic Neuropathy
Reports early onset optic neuropathy

A follow up par
Sources: Literature, Research

Created: 27 Nov 2025, 8:59 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
optic neuropathy; optic atrophy; LHON; LHON-like

Publications

• PMID: 38790159
• PMID: 40465263

Mode of pathogenicity
Other