NDUFS2
Chr 1NADH:ubiquinone oxidoreductase core subunit S2
Also known as: CI-49, LHONAR2, MC1DN6
The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Mammalian mitochondrial complex I is composed of at least 43 different subunits, 7 of which are encoded by the mitochondrial genome, and the rest are the products of nuclear genes. The iron-sulfur protein fraction of complex I is made up of 7 subunits, including this gene product. Complex I catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
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.1
This gene — mechanism propensity
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.
References
ClinVar Variant Classifications
320 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 | 3 | 3 | 0 | 0 | 6 |
Likely Pathogenic | 5 | 2 | 0 | 0 | 7 |
VUS | 1 | 126 | 21 | 6 | 154 |
Likely Benign | 1 | 7 | 47 | 36 | 91 |
Benign | 0 | 1 | 15 | 1 | 17 |
Conflicting | — | 28 | |||
| Total | 10 | 139 | 83 | 43 | 303 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →12 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap NDUFS2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
NDUFS2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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