NDUFS2

Chr 1AR

NADH:ubiquinone oxidoreductase core subunit S2

Also known as: CI-49, LHONAR2, MC1DN6

NCBI Gene: 4720 ENSG00000158864 UniProt: O75306 OMIM: 602985

The protein is a core subunit of mitochondrial complex I that catalyzes electron transfer from NADH through the respiratory chain and is essential for both complex I catalytic activity and assembly. Mutations cause mitochondrial complex I deficiency and Leber-like hereditary optic neuropathy through an autosomal recessive inheritance pattern. The pathogenic mechanism involves loss of function, disrupting mitochondrial energy production.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Mammalian mitochondrial complex I is composed of at least 43 different subunits, 7 of which are encoded by the mitochondrial genome, and the rest are the products of nuclear genes. The iron-sulfur protein fraction of complex I is made up of 7 subunits, including this gene product. Complex I catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Leber-like hereditary optic neuropathy, autosomal recessive 2MIM #620569

Mitochondrial complex I deficiency, nuclear type 6MIM #618228

Clinical highlights

Gene-disease validity (ClinGen)

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

Interpreting a novel variant

Loss of function is the established mechanism 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

0.56

LOEUF

LOF

Mechanism· annotated

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GeneReview available — NDUFS2