NDUFS6
Protein-coding gene in the species Homo sapiens
From Wikipedia, the free encyclopedia
NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial is an enzyme that in humans is encoded by the NDUFS6 gene.[5][6]
Function
The multisubunit NADH:ubiquinone oxidoreductase (complex I) is the first enzyme complex in the electron transport chain of mitochondria. The iron-sulfur protein (IP) fraction is made up of 7 subunits, including NDUFS6.[6]
Clinical significance
Mutations in the NDUFS6 gene are associated with mitochondrial Complex I deficiency, and are inherited in an autosomal recessive manner. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders.[7][8] Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype-phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible.[9] However, the majority of cases are caused by mutations in nuclear-encoded genes.[10][11] It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.[12]
In NDUFS6 mutations the presentation is typically a neonatal lactic acidosis that is swiftly fatal, coupled with multi-system failure.[7][9][12]
