NDUFA1

Chr XXLR

NADH:ubiquinone oxidoreductase subunit A1

Also known as: CI-MWFE, MC1DN12, MWFE, ZNF183

NCBI Gene: 4694 ENSG00000125356 UniProt: O15239 OMIM: 300078

This protein is an essential component of mitochondrial respiratory complex I that transfers electrons from NADH to ubiquinone and anchors the complex to the inner mitochondrial membrane. Mutations cause mitochondrial complex I deficiency, nuclear type 12, which follows X-linked recessive inheritance. The pathogenic mechanism involves dominant-negative effects where mutant proteins disrupt normal complex I assembly and function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The human NDUFA1 gene codes for an essential component of complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha-helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and might act as an anchor for the NADH:ubiquinone oxidoreductase complex at the inner mitochondrial membrane. However, the NDUFA1 peptide is one of about 31 components of the "hydrophobic protein" (HP) fraction of complex I which is involved in proton translocation. Thus the NDUFA1 peptide may also participate in that function. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 12MIM #301020

XLR

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · XLModerateconsider 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

1.18

LOEUF

LOF

Mechanism· G2P

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GeneReview available — NDUFA1