Genetic disorders coupled to ROS deficiency

Redox Biol. 2015 Dec:6:135-156. doi: 10.1016/j.redox.2015.07.009. Epub 2015 Jul 17.


Maintaining the redox balance between generation and elimination of reactive oxygen species (ROS) is critical for health. Disturbances such as continuously elevated ROS levels will result in oxidative stress and development of disease, but likewise, insufficient ROS production will be detrimental to health. Reduced or even complete loss of ROS generation originates mainly from inactivating variants in genes encoding for NADPH oxidase complexes. In particular, deficiency in phagocyte Nox2 oxidase function due to genetic variants (CYBB, CYBA, NCF1, NCF2, NCF4) has been recognized as a direct cause of chronic granulomatous disease (CGD), an inherited immune disorder. More recently, additional diseases have been linked to functionally altered variants in genes encoding for other NADPH oxidases, such as for DUOX2/DUOXA2 in congenital hypothyroidism, or for the Nox2 complex, NOX1 and DUOX2 as risk factors for inflammatory bowel disease. A comprehensive overview of novel developments in terms of Nox/Duox-deficiency disorders is presented, combined with insights gained from structure-function studies that will aid in predicting functional defects of clinical variants.

Keywords: Chronic granulomatous disease; DUOX; Genetic disease; Hypothyroidism; Inflammatory bowel disease; NADPH oxidase; NOX; Reactive oxygen species (ROS).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cardiovascular Diseases / enzymology
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / pathology
  • Diabetes Mellitus / enzymology
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / pathology
  • Dual Oxidases
  • Gene Expression
  • Granulomatous Disease, Chronic / enzymology
  • Granulomatous Disease, Chronic / genetics*
  • Granulomatous Disease, Chronic / pathology
  • Humans
  • Hypothyroidism / enzymology
  • Hypothyroidism / genetics*
  • Hypothyroidism / pathology
  • Inflammatory Bowel Diseases / enzymology
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / pathology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Mutation
  • NADPH Oxidase 1
  • NADPH Oxidase 2
  • NADPH Oxidases / deficiency
  • NADPH Oxidases / genetics
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism


  • DUOXA2 protein, human
  • Membrane Glycoproteins
  • Membrane Proteins
  • Reactive Oxygen Species
  • Dual Oxidases
  • CYBB protein, human
  • NADPH Oxidase 1
  • NADPH Oxidase 2
  • NADPH Oxidases
  • NOX1 protein, human
  • DUOX2 protein, human