NDUFS1
NADH:Ubiquinone Oxidoreductase Core Subunit S1
Gene Information Card
| Symbol | NDUFS1 |
|---|---|
| Full Name | NADH:Ubiquinone Oxidoreductase Core Subunit S1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q33.3 |
| NCBI Gene ID | 4719 ncbi.nlm.nih.gov/gene/4719 |
| Ensembl ID | ENSG00000123219 |
| UniProt ID | P28331 |
| OMIM ID | 157655 |
| HGNC ID | 7707 |
| Aliases | CI-75K, CI-75k, NDUFS1, PRO1304 |
Description
NDUFS1 encodes the 75 kDa iron-sulfur (Fe-S) subunit of mitochondrial NADH:ubiquinone oxidoreductase (Complex I), the first enzyme complex of the electron transport chain. This core subunit contains two [2Fe-2S] and one [4Fe-4S] clusters essential for electron transfer from NADH to ubiquinone. Mutations in NDUFS1 are a common cause of isolated Complex I deficiency, leading to early-onset mitochondrial encephalopathies such as Leigh syndrome and leukodystrophy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Leigh syndrome | Loss-of-function mutations impair Complex I assembly/activity, reducing ATP production and causing neurodegeneration | ClinVar, OMIM |
| Mitochondrial complex I deficiency, nuclear type 1 | Biallelic pathogenic variants disrupt Fe-S cluster binding or protein stability | OMIM #252010 |
| Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) | Compound heterozygous mutations lead to white matter degeneration | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 18.5 | High |
| Skeletal muscle | 15.2 | High |
| Liver | 12.8 | Medium |
| Brain | 11.4 | Medium |
| Kidney | 10.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 22.3 | High expression |
| HeLa | 19.7 | High expression |
| SH-SY5Y | 16.4 | Medium expression |
| HepG2 | 14.1 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1669G>A (p.Gly557Arg) | Missense | Rare | Reduced Complex I activity; associated with Leigh syndrome |
| c.754C>T (p.Arg252Cys) | Missense | Rare | Impaired Fe-S cluster assembly; mitochondrial encephalopathy |
| c.1267C>T (p.Arg423Trp) | Missense | Rare | Loss of enzymatic activity; leukoencephalopathy |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic missense and nonsense mutations reduce or abolish Complex I activity by disrupting Fe-S cluster coordination or protein folding.
Gain of Function (GOF)
No gain-of-function mutations reported for NDUFS1.
Dominant Negative (DN)
No dominant-negative mutations reported; all known pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
| • NADH dehydrogenase (ubiquinone) activity | • mitochondrial electron transport |
| • NADH to ubiquinone | • iron-sulfur cluster binding |
| • mitochondrial inner membrane | • oxidation-reduction process |
Pathways
• Oxidative phosphorylation (KEGG: hsa00190)
• Respiratory electron transport (Reactome: R-HSA-611105)
• Complex I biogenesis (Reactome: R-HSA-6799198)
Protein Summary
NDUFS1 is a 75 kDa iron-sulfur protein that forms part of the peripheral arm of mitochondrial Complex I. It contains three Fe-S clusters (N1a, N1b, N4) that mediate electron transfer from FMN to ubiquinone. The protein is nuclear-encoded, synthesized in the cytosol, and imported into mitochondria. Defects in NDUFS1 are a major cause of isolated Complex I deficiency, manifesting as Leigh syndrome, leukodystrophy, and other mitochondrial disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NDUFS1 Knockout HEK293 Cell Line | EDJ-KQ3728 | Human | 4719 | Details Get a Quote |
| NDUFS1 Knockout HeLa Cell Line | EDJ-KQ24409 | Human | 4719 | Details Get a Quote |
| NDUFS1 Knockout A-549 Cell Line | EDJ-KQ25775 | Human | 4719 | Details Get a Quote |
| NDUFS1 Knockout HCT 116 Cell Line | EDJ-KQ25776 | Human | 4719 | Details Get a Quote |
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