NDUFS6

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NADH dehydrogenase (ubiquinone) Fe-S protein 6, 13kDa (NADH-coenzyme Q reductase)
Identifiers
Symbols NDUFS6 ; CI-13kA; CI-13kD-A; CI13KDA
External IDs OMIM603848 MGI107932 HomoloGene37935 GeneCards: NDUFS6 Gene
EC number 1.6.5.3, 1.6.99.3
RNA expression pattern
PBB GE NDUFS6 203606 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4726 407785
Ensembl ENSG00000145494 ENSMUSG00000021606
UniProt O75380 P52503
RefSeq (mRNA) NM_004553 NM_010888
RefSeq (protein) NP_004544 NP_035018
Location (UCSC) Chr 5:
1.8 – 1.82 Mb
Chr 13:
73.32 – 73.33 Mb
PubMed search [1] [2]

NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial is an enzyme that in humans is encoded by the NDUFS6 gene.[1][2]

Function[edit]

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.[2]

Clinical significance[edit]

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.[3][4] 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.[5] However, the majority of cases are caused by mutations in nuclear-encoded genes.[6][7] 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.[8]Complex I deficiency with autosomal recessive inheritance results from mutation in nuclear-encoded subunit genes, including NDUFV1, NDUFV2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS7, NDUFS8, NDUFA2, NDUFA11, NDUFAF3, NDUFAF10, NDUFB3, NDUFB9, ACAD9, FOXRED1, and MTFMT.

See also[edit]

References[edit]

  1. ^ Emahazion T, Beskow A, Gyllensten U, Brookes AJ (Nov 1998). "Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain". Cytogenetics and Cell Genetics 82 (1-2): 115–9. doi:10.1159/000015082. PMID 9763677. 
  2. ^ a b "Entrez Gene: NDUFS6 NADH dehydrogenase (ubiquinone) Fe-S protein 6, 13kDa (NADH-coenzyme Q reductase)". 
  3. ^ Kirby DM, Salemi R, Sugiana C, Ohtake A, Parry L, Bell KM et al. (Sep 2004). "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency". The Journal of Clinical Investigation 114 (6): 837–45. doi:10.1172/JCI20683. PMID 15372108. 
  4. ^ McFarland R, Kirby DM, Fowler KJ, Ohtake A, Ryan MT, Amor DJ et al. (Jan 2004). "De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency". Annals of Neurology 55 (1): 58–64. doi:10.1002/ana.10787. PMID 14705112. 
  5. ^ Haack TB, Haberberger B, Frisch EM, Wieland T, Iuso A, Gorza M et al. (Apr 2012). "Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing". Journal of Medical Genetics 49 (4): 277–83. doi:10.1136/jmedgenet-2012-100846. PMID 22499348. 
  6. ^ Loeffen JL, Smeitink JA, Trijbels JM, Janssen AJ, Triepels RH, Sengers RC et al. (2000). "Isolated complex I deficiency in children: clinical, biochemical and genetic aspects". Human Mutation 15 (2): 123–34. doi:10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P. PMID 10649489. 
  7. ^ Triepels RH, Van Den Heuvel LP, Trijbels JM, Smeitink JA (2001). "Respiratory chain complex I deficiency". American Journal of Medical Genetics 106 (1): 37–45. doi:10.1002/ajmg.1397. PMID 11579423. 
  8. ^ Robinson BH (May 1998). "Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect". Biochimica Et Biophysica Acta 1364 (2): 271–86. PMID 9593934. 

Further reading[edit]