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NADH dehydrogenase (ubiquinone) Fe-S protein 3, 30kDa (NADH-coenzyme Q reductase)
Symbols NDUFS3 ; CI-30
External IDs OMIM603846 MGI1915599 HomoloGene3346 GeneCards: NDUFS3 Gene
EC number,
RNA expression pattern
PBB GE NDUFS3 201740 at tn.png
More reference expression data
Species Human Mouse
Entrez 4722 68349
Ensembl ENSG00000213619 ENSMUSG00000005510
UniProt O75489 Q9DCT2
RefSeq (mRNA) NM_004551 NM_026688
RefSeq (protein) NP_004542 NP_080964
Location (UCSC) Chr 11:
47.59 – 47.61 Mb
Chr 2:
90.89 – 90.9 Mb
PubMed search [1] [2]

NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial is an enzyme that in humans is encoded by the NDUFS3 gene.[1][2]


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 of complex I is made up of 7 subunits.[2]

Clinical significance[edit]

Mutations in the NDUFS3 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]

Model organisms[edit]

Model organisms have been used in the study of NDUFS3 function. A conditional knockout mouse line, called Ndufs3tm1a(EUCOMM)Wtsi[17][18] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[19][20][21]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[15][22] Twenty five tests were carried out on mutant mice and six significant abnormalities were observed.[15] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; males had an increased lean body mass and heart weight, and a decrease in some plasma chemistry and haematology parameters.[15]

See also[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: NDUFS3 NADH dehydrogenase (ubiquinone) Fe-S protein 3, 30kDa (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. 
  9. ^ "DEXA data for Ndufs3". Wellcome Trust Sanger Institute. 
  10. ^ "Clinical chemistry data for Ndufs3". Wellcome Trust Sanger Institute. 
  11. ^ "Haematology data for Ndufs3". Wellcome Trust Sanger Institute. 
  12. ^ "Heart weight data for Ndufs3". Wellcome Trust Sanger Institute. 
  13. ^ "Salmonella infection data for Ndufs3". Wellcome Trust Sanger Institute. 
  14. ^ "Citrobacter infection data for Ndufs3". Wellcome Trust Sanger Institute. 
  15. ^ a b c d Gerdin, AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. 
  16. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  17. ^ "International Knockout Mouse Consortium". 
  18. ^ "Mouse Genome Informatics". 
  19. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V et al. (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750. 
  20. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  21. ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  22. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 

Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma Suhane S, Berel D and Ramanujan VK Biochem Biophys Res Commun 2011 Sep 9; 412(4): 590-595 doi: 10.1016/j.bbrc.2011.08.003. Epub 2011 Aug 16

Further reading[edit]