NDUFS2
Chr 1ARNADH:ubiquinone oxidoreductase core subunit S2
Also known as: CI-49, LHONAR2, MC1DN6
The protein is a core subunit of mitochondrial complex I that catalyzes electron transfer from NADH through the respiratory chain and is essential for both complex I catalytic activity and assembly. Mutations cause mitochondrial complex I deficiency and Leber-like hereditary optic neuropathy through an autosomal recessive inheritance pattern. The pathogenic mechanism involves loss of function, disrupting mitochondrial energy production.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
Core iron-sulfur subunit of mitochondrial complex I. Biallelic LOF causes complex I deficiency. This is an autosomal recessive LOF gene; the Badonyi DN prediction is incorrect.
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
200 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 2 | 1 | 5 | 0 | 8 |
Likely Pathogenic | 3 | 1 | 1 | 0 | 5 |
VUS | 0 | 75 | 12 | 5 | 92 |
Likely Benign | 0 | 4 | 33 | 18 | 55 |
Benign | 0 | 1 | 13 | 0 | 14 |
Conflicting | — | 11 | |||
| Total | 5 | 82 | 64 | 23 | 185 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NDUFS2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools