NDUFS8

Chr 11

NADH:ubiquinone oxidoreductase core subunit S8

Also known as: CI-23k, CI23KD, MC1DN2, TYKY

NCBI Gene: 4728 ENSG00000110717 UniProt: O00217

The protein is a subunit of mitochondrial Complex I that binds iron-sulfur clusters and is required for electron transfer in the respiratory chain. Mutations cause mitochondrial complex I deficiency and Leigh syndrome through autosomal recessive inheritance. The pathogenic mechanism involves impaired NADH oxidation and disrupted mitochondrial energy production.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a subunit of mitochondrial NADH:ubiquinone oxidoreductase, or Complex I, a multimeric enzyme of the respiratory chain responsible for NADH oxidation, ubiquinone reduction, and the ejection of protons from mitochondria. The encoded protein is involved in the binding of two of the six to eight iron-sulfur clusters of Complex I and, as such, is required in the electron transfer process. Mutations in this gene have been associated with Leigh syndrome. [provided by RefSeq, Mar 2010]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMitochondrial complex I deficiency, nuclear type 2

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARModerateconsider for supplementary testing2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.74

LOEUF

LOF

Mechanism· G2P

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GeneReview available — NDUFS8