NDUFS6: A Core Subunit of Mitochondrial Complex I
Genetic variants in NDUFS6 cause mitochondrial complex I deficiency and are associated with Leigh syndrome and other early-onset neurological disorders.
Gene Information Card
| Symbol | NDUFS6 |
|---|---|
| Full Name | NADH:ubiquinone oxidoreductase core subunit S6 |
| Gene Type | Protein coding |
| Chromosomal Location | 5p15.33 |
| NCBI Gene ID | 4726 ncbi.nlm.nih.gov/gene/4726 |
| Ensembl ID | ENSG00000145494 |
| UniProt ID | O75380 |
| OMIM ID | 603848 |
| HGNC ID | 7711 |
| Aliases | CI-13kD-A, CI13KDA, NADH dehydrogenase (ubiquinone) Fe-S protein 6 |
Description
The NDUFS6 gene encodes a 13 kDa core subunit of mitochondrial NADH:ubiquinone oxidoreductase (Complex I), the first enzyme of the electron transport chain. This nuclear-encoded protein is essential for Complex I assembly and catalytic activity. Mutations in NDUFS6 cause mitochondrial complex I deficiency, a severe disorder often presenting as Leigh syndrome, with early-onset neurodegeneration, lactic acidosis, and respiratory chain dysfunction.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex I deficiency, nuclear type 9 (MC1DN9) | Loss-of-function mutations in NDUFS6 impair Complex I assembly and activity, disrupting oxidative phosphorylation and ATP production. | ClinVar, OMIM #618232 |
| Leigh syndrome | Biallelic NDUFS6 variants lead to Leigh syndrome, characterized by bilateral necrotizing lesions in the basal ganglia and brainstem. | OMIM #256000, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 28.5 | High |
| Skeletal muscle | 22.1 | High |
| Liver | 15.3 | Medium |
| Brain | 12.8 | Medium |
| Kidney | 10.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.2 | Embryonic kidney cells |
| HeLa | 14.7 | Cervical cancer cells |
| HepG2 | 12.1 | Hepatocellular carcinoma cells |
| SH-SY5Y | 9.8 | Neuroblastoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.184C>T (p.Arg62Ter) | Nonsense | Rare | Premature stop codon; loss of protein function; associated with Leigh syndrome |
| c.310G>A (p.Gly104Arg) | Missense | Rare | Impairs Complex I assembly and activity |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of translation initiation; complete loss of NDUFS6 |
Mutation functional classification
Loss of Function (LOF)
Most NDUFS6 mutations are loss-of-function, leading to reduced or absent Complex I activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects described; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • NADH dehydrogenase (ubiquinone) activity (GO:0008137) | • mitochondrial respiratory chain complex I assembly (GO:0032981) |
| • mitochondrial inner membrane (GO:0005743) | • oxidation-reduction process (GO:0055114) |
Pathways
• Oxidative phosphorylation (KEGG:00190)
• Respiratory electron transport (Reactome:R-HSA-611105)
• Complex I biogenesis (Reactome:R-HSA-6799198)
Protein Summary
NDUFS6 is a 13.4 kDa iron-sulfur (Fe-S) cluster-containing subunit of mitochondrial Complex I. It is located in the peripheral arm of the complex and participates in electron transfer from NADH to ubiquinone. The protein is synthesized in the cytosol and imported into mitochondria, where it integrates into the holoenzyme. Defects in NDUFS6 disrupt Complex I assembly, leading to energy deficiency and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NDUFS6 Knockout HEK293 Cell Line | EDJ-KQ5325 | Human | 4726 | Details Get a Quote |
| NDUFS6 Knockout A-549 Cell Line | EDJ-KQ28411 | Human | 4726 | Details Get a Quote |
| NDUFS6 Knockout HCT 116 Cell Line | EDJ-KQ28412 | Human | 4726 | Details Get a Quote |
| NDUFS6 Knockout HeLa Cell Line | EDJ-KQ28413 | Human | 4726 | Details Get a Quote |
