Optic neuropathy

Gene: NDUFS1

Amber List (moderate evidence)

NDUFS1 (NADH:ubiquinone oxidoreductase core subunit S1)
EnsemblGeneIds (GRCh38): ENSG00000023228
EnsemblGeneIds (GRCh37): ENSG00000023228
OMIM: 157655, Gene2Phenotype
NDUFS1 is in 15 panels

2 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are now 3 unrelated cases reported with biallelic NDUFS1 variants and optic neuropathy (LHON-like or syndromic CI-deficiency presentation). Hence, this gene should be promoted to Green at the next update.
Created: 27 May 2026, 12:29 p.m. | Last Modified: 27 May 2026, 12:29 p.m.
Panel Version: 6.37
Benit et al. (2001), PMID: 11349233
3 families with AR NDUFS1-related CI deficiency; in 1 of these families (family 4), symptoms included OA. Proband 4 was comp het for NDUFS1 c.664–666del (NM_005006.7:c.666_668del (p.Ile223del)) and c.755A>G, p.Asp252Gly.

Zheng et al. (2025), PMID: 39423307
Large optic atrophy cohort. 2 families with AR OA/LHON-like and NDUFS1 comp het variants: p.Arg158His/p.Asp138Ala and p.His66Leu/p.Ser457Ilefs*7.

NDUFS1 is associated with AR Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226 in OMIM (accessed 27th May 2026).
Created: 27 May 2026, 12:28 p.m. | Last Modified: 27 May 2026, 12:28 p.m.
Panel Version: 6.36

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226

Publications

Tom Cullup (Great Ormond Street Hospital)

Red List (low evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 5, 618226

History Filter Activity

27 May 2026, Gel status: 2

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: NDUFS1 were set to

27 May 2026, Gel status: 2

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226 to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226

27 May 2026, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: ndufs1 has been classified as Amber List (Moderate Evidence).

27 May 2026, Gel status: 1

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q2_26_promote_green tag was added to gene: NDUFS1.

13 Apr 2023, Gel status: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: NDUFS1 were changed from MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 5, 618226 to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226

19 Mar 2019, Gel status: 1

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: NDUFS1 were changed from to MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 5, 618226

19 Mar 2019, Gel status: 1

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: NDUFS1 was changed from to BIALLELIC, autosomal or pseudoautosomal

19 Mar 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Ivone Leong (Genomics England Curator)

gene: NDUFS1 was added gene: NDUFS1 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red Mode of inheritance for gene: NDUFS1 was set to