NDUFS4
Chr 5ARNADH:ubiquinone oxidoreductase subunit S4
Also known as: AQDQ, CI-18, CI-18 kDa, CI-AQDQ, MC1DN1
The protein functions as a nuclear-encoded accessory subunit of mitochondrial complex I (NADH dehydrogenase), which removes electrons from NADH and transfers them to ubiquinone in the electron transport chain. Autosomal recessive mutations cause mitochondrial complex I deficiency, which can present as Leigh syndrome and other mitochondrial disorders. The pathogenic mechanism involves dominant-negative effects that disrupt normal complex I assembly and function.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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
269 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 | 17 | 0 | 13 | 0 | 30 |
Likely Pathogenic | 28 | 1 | 1 | 0 | 30 |
VUS | 2 | 55 | 10 | 1 | 68 |
Likely Benign | 0 | 4 | 47 | 43 | 94 |
Benign | 0 | 0 | 25 | 3 | 28 |
Conflicting | — | 9 | |||
| Total | 47 | 60 | 96 | 47 | 259 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NDUFS4 · 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