NDUFS4

Chr 5AR

NADH:ubiquinone oxidoreductase subunit S4

Also known as: AQDQ, CI-18, CI-18 kDa, CI-AQDQ, MC1DN1

NCBI Gene: 4724 ENSG00000164258 UniProt: O43181 OMIM: 602694

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes an nuclear-encoded accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I, or NADH:ubiquinone oxidoreductase). Complex I removes electrons from NADH and passes them to the electron acceptor ubiquinone. Mutations in this gene can cause mitochondrial complex I deficiencies such as Leigh syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 1MIM #252010

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.16

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — NDUFS4