NDUFS6

NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial is an is_associated_with::enzyme that in humans is encoded by the NDUFS6 is_associated_with::gene.

Function
The multisubunit NADH:ubiquinone oxidoreductase (is_associated_with::complex I) is the first enzyme complex in the is_associated_with::electron transport chain of mitochondria. The is_associated_with::iron-sulfur protein (IP) fraction is made up of 7 subunits, including NDUFS6.

Clinical significance
Mutations in the NDUFS6 gene are associated with Mitochondrial Complex I Deficiency, which is autosomal recessive. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders. 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. However, the majority of cases are caused by mutations in nuclear-encoded genes. 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. Complex I deficiency with autosomal recessive inheritance results from mutation in nuclear-encoded subunit genes, including is_associated_with::NDUFV1, is_associated_with::NDUFV2, is_associated_with::NDUFS1, is_associated_with::NDUFS2, is_associated_with::NDUFS3, is_associated_with::NDUFS4, is_associated_with::NDUFS7, is_associated_with::NDUFS8, is_associated_with::NDUFA2, is_associated_with::NDUFA11, is_associated_with::NDUFAF3, is_associated_with::NDUFAF10, is_associated_with::NDUFB3, is_associated_with::NDUFB9, is_associated_with::ACAD9, is_associated_with::FOXRED1, and is_associated_with::MTFMT.