NDUFS8: NADH:Ubiquinone Oxidoreductase Core Subunit S8
A critical component of mitochondrial Complex I, associated with Leigh syndrome and mitochondrial respiratory chain disorders.
Gene Information Card
| Symbol | NDUFS8 |
|---|---|
| Full Name | NADH:Ubiquinone Oxidoreductase Core Subunit S8 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q13.2 |
| NCBI Gene ID | 4728 ncbi.nlm.nih.gov/gene/4728 |
| Ensembl ID | ENSG00000110719 |
| UniProt ID | P21912 |
| OMIM ID | 602141 |
| HGNC ID | 7708 |
| Aliases | CI-23kD, CI-23kDa, Complex I-23kD, NADH-ubiquinone oxidoreductase 23 kDa subunit |
Description
NDUFS8 encodes a 23 kDa subunit of the 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 activity. Mutations in NDUFS8 are associated with Leigh syndrome and other mitochondrial encephalopathies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Leigh syndrome | Loss-of-function mutations impair Complex I activity, leading to ATP deficiency and neurodegeneration. | ClinVar, OMIM |
| Mitochondrial complex I deficiency, nuclear type 2 | Biallelic pathogenic variants cause isolated Complex I deficiency. | OMIM #618222 |
| Encephalopathy, progressive, with leukodystrophy | Severe neurological deterioration linked to NDUFS8 mutations. | PubMed, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Skeletal muscle | 10.2 | Medium |
| Liver | 8.1 | Medium |
| Brain | 7.4 | Medium |
| Kidney | 6.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | High expression |
| HeLa | 12.1 | Medium expression |
| K-562 | 9.8 | Medium expression |
| HepG2 | 8.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.305G>A (p.Arg102Gln) | Missense | Rare | Reduces Complex I activity; associated with Leigh syndrome |
| c.364C>T (p.Arg122Trp) | Missense | Rare | Impairs subunit stability and assembly |
| c.424G>A (p.Glu142Lys) | Missense | Very rare | Decreased enzyme activity; reported in mitochondrial encephalopathy |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic missense and nonsense mutations reduce or abolish Complex I activity.
Gain of Function (GOF)
Not described for NDUFS8.
Dominant Negative (DN)
Not reported; disease is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • NADH dehydrogenase (ubiquinone) activity | • mitochondrial respiratory chain complex I |
| • electron transport chain | • 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
NDUFS8 is a 23 kDa nuclear-encoded subunit of mitochondrial Complex I. It is part of the iron-sulfur (IP) fragment of the enzyme and participates in electron transfer from NADH to ubiquinone. The protein is imported into mitochondria and assembled into the holoenzyme. Defects in NDUFS8 cause Complex I deficiency, leading to Leigh syndrome and other mitochondrial disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NDUFS8 Knockout HEK293 Cell Line | EDJ-KQ5322 | Human | 4728 | Details Get a Quote |
| NDUFS8 Knockout HeLa Cell Line | EDJ-KQ27175 | Human | 4728 | Details Get a Quote |
| NDUFS8 Knockout A-549 Cell Line | EDJ-KQ28406 | Human | 4728 | Details Get a Quote |
| NDUFS8 Knockout HCT 116 Cell Line | EDJ-KQ28407 | Human | 4728 | Details Get a Quote |
