SOD1

SOD1 encodes Cu/Zn superoxide dismutase, a highly abundant homodimeric metalloenzyme that catalyzes the dismutation of superoxide radical (O2.-) into molecular oxygen and hydrogen peroxide (EC 1.15.1.1), providing a first line of antioxidant defense. Each ~16 kDa subunit adopts an eight-stranded Greek-key beta-barrel and binds one catalytic copper ion and one structural zinc ion; an intrasubunit disulfide bond (Cys58-Cys147) and zinc binding stabilize the unusually robust dimer. Catalytic copper is delivered by the copper chaperone CCS, which also promotes intramolecular disulfide formation during maturation. SOD1 is predominantly cytosolic, with a functional minor pool in the mitochondrial intermembrane space (imported with CCS) that detoxifies mitochondria-derived superoxide, and additional pools detected in the nucleus and extracellularly. Beyond its dismutase activity, SOD1 has been reported to oxidize hydrogen sulfide to sulfate (a reactive-sulfur-species detoxifying activity) and to act as a redox sensor that binds Rac1 to modulate NADPH oxidase. Loss of SOD1 activity causes a recessive neurological syndrome (STAHP), whereas dominant missense variants cause familial amyotrophic lateral sclerosis through a toxic gain-of-function involving destabilization, misfolding, and aggregation of the protein.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.